02566nas a2200385 4500008004100000022001400041245011500055210006900170260001300239300001100252490000700263520149700270653003901767653000901806653001001815653001901825653001501844653004001859653001101899653001101910653001701921653001101938653000901949653002401958653002601982653001702008653001202025653002202037100001702059700002002076700001602096700001702112700001602129856003502145 2000 eng d a0085-253800aTobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population.0 aTobacco hypertension and vascular disease risk factors for renal c2000 May a2072-90 v573 a
BACKGROUND: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population.
METHODS: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase.
RESULTS: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness.
CONCLUSIONS: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.
10aAfrican Continental Ancestry Group10aAged10aAging10aCohort Studies10aCreatinine10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension10aKidney10aMale10aRegression Analysis10aRetrospective Studies10aRisk Factors10aSmoking10aVascular Diseases1 aBleyer, A, J1 aShemanski, L, R1 aBurke, G, L1 aHansen, K, J1 aAppel, R, G uhttps://chs-nhlbi.org/node/61403244nas a2200349 4500008004100000022001400041245012500055210006900180260001300249300001000262490000700272520223000279653000902509653001902518653001102537653001102548653001702559653001102576653002002587653000902607653002402616653003702640653002202677100002402699700002502723700002302748700002202771700002302793700002202816700002102838856003502859 2003 eng d a1523-683800aRelationships between renovascular disease, blood pressure, and renal function in the elderly: a population-based study.0 aRelationships between renovascular disease blood pressure and re c2003 May a990-60 v413 aBACKGROUND: The purpose of this study is to examine the associations between renovascular disease (RVD) and cross-sectional measures of blood pressure and renal function among participants in the Cardiovascular Health Study (CHS).
METHODS: The CHS is a prospective cohort study of cardiovascular disease among elderly Americans. As part of an ancillary study, participants in the Forsyth County, NC, cohort of the CHS were invited to undergo renal duplex sonography (RDS) to define the presence or absence of RVD (defined as any focal peak systolic velocity > or = 1.8 milliseconds or the absence of a Doppler shifted signal from an imaged artery). Demographic, risk factor, blood pressure, and serum creatinine data were obtained at the time of RDS and from the annual CHS examination.
RESULTS: Eight hundred thirty-four CHS participants (including 525 women [63%], 309 men [37%], 194 African Americans [23%], and 635 Caucasians [76%]) with a mean age of 77.2 +/- 4.9 years underwent successful RDS. RVD was present in 57 participants (6.8%). When examined according to the presence or absence of RVD, significant univariate differences were observed in the prevalence of clinical hypertension (72% versus 50%; P = 0.001), systolic blood pressure (145 versus 136 mm Hg; P = 0.001), and renal insufficiency (16% versus 8%; P = 0.041). Multivariate analyses showed significant and independent associations for the presence of RVD with increasing systolic blood pressure (P = 0.034), clinical hypertension (odds ratio, 2.68; 95% confidence interval, 1.44 to 4.99; P = 0.002), increasing serum creatinine level, and renal insufficiency (odds ratio, 2.21; 95% confidence interval, 1.02 to 4.79; P = 0.043). A significant interaction was observed between the presence of RVD and increasing systolic blood pressure in association with increasing serum creatinine levels (P = 0.041).
CONCLUSION: These results suggest important population-based associations between RVD and cross-sectional measures of blood pressure and renal function. Furthermore, the observed relationship between RVD and increasing serum creatinine level was influenced strongly by increasing blood pressure.
10aAged10aBlood Pressure10aFemale10aHumans10aHypertension10aKidney10aKidney Diseases10aMale10aProspective Studies10aUltrasonography, Doppler, Duplex10aVascular Diseases1 aEdwards, Matthew, S1 aHansen, Kimberley, J1 aCraven, Timothy, E1 aCherr, Gregory, S1 aBleyer, Anthony, J1 aBurke, Gregory, L1 aDean, Richard, H uhttps://chs-nhlbi.org/node/73702977nas a2200373 4500008004100000022001400041245011400055210006900169260001300238300001200251490000700263520191600270653000902186653002202195653002802217653001502245653001302260653002302273653001102296653001102307653001102318653002002329653000902349653001202358653003202370100002402402700002402426700003202450700002202482700002502504700002002529700001902549856003502568 2004 eng d a1046-667300aModerate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.0 aModerate renal impairment and risk of dementia among older adult c2004 Jul a1904-110 v153 aRenal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.
10aAged10aAlzheimer Disease10aCardiovascular Diseases10aCreatinine10aDementia10aDementia, Vascular10aFemale10aHumans10aKidney10aKidney Diseases10aMale10aMuscles10aProportional Hazards Models1 aSeliger, Stephen, L1 aSiscovick, David, S1 aStehman-Breen, Catherine, O1 aGillen, Daniel, L1 aFitzpatrick, Annette1 aBleyer, Anthony1 aKuller, Lew, H uhttps://chs-nhlbi.org/node/79504369nas a2200529 4500008004100000022001400041245015000055210006900205260001300274300001100287490000700298520286400305653002203169653000903191653002203200653001003222653002803232653001603260653001903276653001603295653001503311653002203326653002403348653004003372653001103412653003103423653001103454653001703465653001103482653000903493653001603502653002403518653001603542653001103558653002103569653002003590100002403610700002103634700002303655700002303678700002003701700001803721700001803739700002203757700002503779856003503804 2005 eng d a1523-683800aAssociations between retinal microvascular abnormalities and declining renal function in the elderly population: the Cardiovascular Health Study.0 aAssociations between retinal microvascular abnormalities and dec c2005 Aug a214-240 v463 aBACKGROUND: Microvascular abnormalities in the kidney are common histopathologic findings in individuals with chronic kidney disease or renal failure. These abnormalities may represent one manifestation of ongoing systemic microvascular damage. We hypothesized that retinal microvascular abnormalities, when present, would be associated with progressive renal dysfunction in elderly individuals.
METHODS: The Cardiovascular Health Study (CHS) is a prospective, multicenter, cohort study initiated in 1989 designed to examine cardiovascular risk factors, morbidity, and mortality in elderly Americans. As part of an ancillary study, CHS participants underwent retinal photography in 1997 and 1998. Retinal microvascular abnormalities were assessed and graded by using standardized measures. Retinal microvascular abnormalities were defined as retinopathy (hard and soft exudates, hemorrhages, or microaneurysms) and/or retinal arteriolar abnormalities (arteriovenous nicking, focal arteriolar narrowing, or lowest quartile arteriole-venule ratio). Associations between these abnormalities and observed 4-year changes in serum creatinine levels and estimated glomerular filtration rates (eGFRs) from study years 5 to 9 (encompassing years 1994 to 2001) were examined by using regression modeling.
RESULTS: A total of 1,394 CHS participants had retinal and serum creatinine data. After adjustments for age, race, sex, weight, diabetes, hypertension, angiotensin-converting enzyme inhibitor use, and proteinuria, participants with retinopathy showed a significant increase in serum creatinine level and decline in eGFR compared with those without retinopathy during the 4-year study period (+0.24 mg/dL [+21 micromol/L] versus -0.21 mg/dL [-19 micromol/L] and -0.48 mL/min/1.73 m2 [-0.01 mL/s/1.73 m2] versus +1.74 mL/min/1.73 m2 [+0.03 mL/s/1.73 m2], respectively). Participants with retinopathy also were significantly more likely to have an observed significant deterioration in renal function, defined as a 0.3-mg/dL (27-micromol/L) increase in serum creatinine level or 20% or greater decline in eGFR (odds ratio, 3.20; 95% confidence interval, 1.58 to 6.50; and odds ratio, 2.84; 95% confidence interval, 1.56 to 5.16, respectively). These associations remained in separate stratified analyses of patients with and without diabetes. The presence of retinal arteriolar abnormalities was not associated with deteriorating renal function.
CONCLUSION: Retinal microvascular abnormalities defined as retinopathy were significantly associated with renal function deterioration. The observed findings were independent of effects of any associated diabetes or hypertension. These findings suggest that systemic microvascular disease may be associated with progressive renal dysfunction in the elderly population.
10aAfrican Americans10aAged10aAged, 80 and over10aAging10aAntihypertensive Agents10aCapillaries10aCohort Studies10aComorbidity10aCreatinine10aDiabetes Mellitus10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney10aMale10aPhotography10aProspective Studies10aProteinuria10aRetina10aRetinal Diseases10aRetinal Vessels1 aEdwards, Matthew, S1 aWilson, David, B1 aCraven, Timothy, E1 aStafford, Jeanette1 aFried, Linda, F1 aWong, Tien, Y1 aKlein, Ronald1 aBurke, Gregory, L1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/85403216nas a2200445 4500008004100000022001400041245008600055210006900141260001600210300001200226490000800238520200500246653000902251653001502260653002802275653003302303653001502336653001502351653001402366653001102380653002202391653003102413653001102444653001102455653002002466653000902486653001402495653002602509653001402535653000902549100002402558700002002582700001602602700002002618700002402638700002002662700002402682700002902706856003502735 2005 eng d a1533-440600aCystatin C and the risk of death and cardiovascular events among elderly persons.0 aCystatin C and the risk of death and cardiovascular events among c2005 May 19 a2049-600 v3523 aBACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community.
METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c).
RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes.
CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.
10aAged10aBiomarkers10aCardiovascular Diseases10aCerebrospinal Fluid Proteins10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMortality10aMultivariate Analysis10aPrognosis10aRisk1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSeliger, Stephen, L1 aNewman, Anne, B1 aSiscovick, David, S1 aStehman-Breen, Catherine uhttps://chs-nhlbi.org/node/84003555nas a2200445 4500008004100000022001400041245008100055210006900136260001600205300001200221490000800233520234700241653000902588653001502597653001502612653001502627653001402642653001102656653002202667653003102689653001802720653001102738653001402749653001102763653002602774653000902800653001702809653001802826100002002844700001602864700003202880700002002912700002502932700002002957700002002977700002102997700002403018710003203042856003503074 2005 eng d a1539-370400aCystatin C concentration as a risk factor for heart failure in older adults.0 aCystatin C concentration as a risk factor for heart failure in o c2005 Apr 05 a497-5050 v1423 aBACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.
OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.
DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.
SETTING: Adults 65 years of age or older from 4 communities in the United States.
PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.
MEASUREMENTS: Incident heart failure.
RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).
LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.
CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.
10aAged10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney10aKidney Function Tests10aMale10aRisk Factors10aUnited States1 aSarnak, Mark, J1 aKatz, Ronit1 aStehman-Breen, Catherine, O1 aFried, Linda, F1 aJenny, Nancy, Swords1 aPsaty, Bruce, M1 aNewman, Anne, B1 aSiscovick, David1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/82703279nas a2200541 4500008004100000022001400041245008300055210006900138260001300207300001100220490000700231520176200238653002202000653000902022653001002031653002102041653001902062653002802081653001902109653001502128653002802143653001302171653002402184653004002208653001102248653001102259653003102270653001102301653002002312653002602332653000902358653001702367653002902384653002202413653001702435653002102452653001202473653003702485653001802522100002302540700002402563700002302587700002402610700002202634700002102656700002502677856003502702 2005 eng d a1523-683800aRenal duplex parameters, blood pressure, and renal function in elderly people.0 aRenal duplex parameters blood pressure and renal function in eld c2005 May a842-500 v453 aBACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans.
METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques.
RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine.
CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.
10aAfrican Americans10aAged10aAging10aArteriosclerosis10aBlood Pressure10aCardiovascular Diseases10aCohort Studies10aCreatinine10aCross-Sectional Studies10aDiastole10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aHumans10aHypertension, Renovascular10aKidney10aKidney Diseases10aKidney Function Tests10aMale10aRenal Artery10aRenal Artery Obstruction10aRenal Circulation10aRisk Factors10aSampling Studies10aSystole10aUltrasonography, Doppler, Duplex10aUnited States1 aPearce, Jeffrey, D1 aEdwards, Matthew, S1 aCraven, Timothy, E1 aEnglish, William, P1 aMondi, Matthew, M1 aReavis, Scott, W1 aHansen, Kimberley, J uhttps://chs-nhlbi.org/node/83604065nas a2200433 4500008004100000022001400041245011900055210006900174260001600243300001100259490000800270520281000278653000903088653001503097653002803112653001503140653001503155653001403170653003103184653001103215653001103226653002503237653001403262653003203276653003303308653001703341100002403358700001603382700002003398700002003418700002003438700002903458700002403487700002203511700001703533700002203550700002403572856003503596 2006 eng d a1539-370400aCystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease.0 aCystatin C and prognosis for cardiovascular and kidney outcomes c2006 Aug 15 a237-460 v1453 aBACKGROUND: Cystatin C is an alternative measure of kidney function that may have prognostic importance among elderly persons who do not meet standard criteria for chronic kidney disease (estimated glomerular filtration rate [GFR] > or =60 mL/min per 1.73 m2).
OBJECTIVE: To evaluate cystatin C as a prognostic biomarker for death, cardiovascular disease, and incident chronic kidney disease among elderly persons without chronic kidney disease.
DESIGN: Cohort study.
SETTING: The Cardiovascular Health Study, a population-based cohort recruited from 4 communities in the United States.
PARTICIPANTS: 4663 elderly persons.
MEASUREMENTS: Measures of kidney function were creatinine-based estimated GFR by using the Modification of Diet in Renal Disease equation and cystatin C concentration. Outcomes were death, cardiovascular death, noncardiovascular death, heart failure, stroke, myocardial infarction, and incident chronic kidney disease during follow-up (median, 9.3 years).
RESULTS: At baseline, 78% of participants did not have chronic kidney disease (estimated GFR > or =60 mL/min per 1.73 m2) and mean cystatin C concentration, creatinine concentration, and estimated GFR were 1.0 mg/L, 79.6 micromol/L (0.9 mg/dL), and 83 mL/min per 1.73 m2, respectively. Cystatin C concentrations (per SD, 0.18 mg/L) had strong associations with death (hazard ratio, 1.33 [95% CI, 1.25 to 1.40]), cardiovascular death (hazard ratio, 1.42 [CI, 1.30 to 1.54]), noncardiovascular death (hazard ratio, 1.26 [CI, 1.17 to 1.36]), incident heart failure (hazard ratio, 1.28 [CI, 1.17 to 1.40]), stroke (hazard ratio, 1.22 [CI, 1.08 to 1.38]), and myocardial infarction (hazard ratio, 1.20 [CI, 1.06 to 1.36]) among these participants. Serum creatinine concentrations had much weaker associations with each outcome and only predicted cardiovascular death. Participants without chronic kidney disease who had elevated cystatin C concentrations (> or =1.0 mg/L) had a 4-fold risk for progressing to chronic kidney disease after 4 years of follow-up compared with those with cystatin C concentrations less than 1.0 mg/L.
LIMITATIONS: Because this study did not directly measure GFR or albuminuria, the extent to which cystatin C may be influenced by nonrenal factors was not determined and participants with albuminuria might have been misclassified as having no kidney disease.
CONCLUSIONS: Among elderly persons without chronic kidney disease, cystatin C is a prognostic biomarker of risk for death, cardiovascular disease, and chronic kidney disease. In this setting, cystatin C seems to identify a "preclinical" state of kidney dysfunction that is not detected with serum creatinine or estimated GFR.
10aAged10aBiomarkers10aCardiovascular Diseases10aCreatinine10aCystatin C10aCystatins10aGlomerular Filtration Rate10aHumans10aKidney10aLongitudinal Studies10aPrognosis10aProportional Hazards Models10aRenal Insufficiency, Chronic10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aNewman, Anne, B1 aStehman-Breen, Catherine1 aSeliger, Stephen, L1 aKestenbaum, Brian1 aPsaty, Bruce1 aTracy, Russell, P1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/91202943nas a2200457 4500008004100000022001400041245007900055210006900134260001300203300001000216490000700226520171800233653000901951653002201960653001501982653001401997653001102011653001802022653001102040653001102051653002802062653002502090653000902115653001702124653002402141653001702165653001602182100002002198700002402218700002402242700002102266700002202287700002902309700001702338700002102355700001902376700001702395700002002412700001802432856003502450 2007 eng d a1046-667300aAssociation of kidney function with incident hip fracture in older adults.0 aAssociation of kidney function with incident hip fracture in old c2007 Jan a282-60 v183 aKidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95% CI 1.01, 1.33) but not in men (HR 1.14; 95% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk.
10aAged10aAged, 80 and over10aCystatin C10aCystatins10aFemale10aHip Fractures10aHumans10aKidney10aKidney Failure, Chronic10aLongitudinal Studies10aMale10aOsteoporosis10aProspective Studies10aRisk Factors10aSex Factors1 aFried, Linda, F1 aBiggs, Mary, Louise1 aShlipak, Michael, G1 aSeliger, Stephen1 aKestenbaum, Bryan1 aStehman-Breen, Catherine1 aSarnak, Mark1 aSiscovick, David1 aHarris, Tamara1 aCauley, Jane1 aNewman, Anne, B1 aRobbins, John uhttps://chs-nhlbi.org/node/93302852nas a2200421 4500008004100000022001400041245009800055210006900153260001300222300001000235490000600245520167800251653000901929653002201938653002401960653002801984653002002012653002102032653002402053653001102077653001102088653001102099653002002110653000902130653002002139100002202159700002002181700002402201700002002225700002002245700001602265700002002281700002102301700002902322700002002351700002402371856003502395 2007 eng d a1555-905X00aKidney function, electrocardiographic findings, and cardiovascular events among older adults.0 aKidney function electrocardiographic findings and cardiovascular c2007 May a501-80 v23 aChronic kidney disease (CKD) is associated with cardiovascular (CV) disease and mortality. It is not known whether cardiac rhythm disturbances are more prevalent among individuals with CKD or whether resting electrocardiogram findings predict future CV events in the CKD setting. Data were obtained from the Cardiovascular Health Study, a community-based study of adults aged >/=65 yr. After exclusions for prevalent heart disease, atrial fibrillation, implantable pacemaker, or antiarrhythmic medication use, 3238 participants were analyzed. CKD was defined by an estimated GFR <60 ml/min per 1.73 m(2). Outcomes were adjudicated incident heart failure (HF), incident coronary heart disease (CHD), and mortality. Participants with CKD had longer PR and corrected QT intervals compared with those without CKD; however, differences in electrocardiographic markers were explained by traditional CV risk factors and CV medication use. After adjustment for known risk factors, each 10-ms increase in the QRS interval was associated with a 15% greater risk for incident HF (95% confidence interval [CI] 1.04 to 1.27), a 13% greater risk for CHD (95% CI 1.04 to 1.24), and a 17% greater risk for mortality (95% CI 1.09, 1.25) among CKD participants. Each 5% increase in QTI was associated with a 42% (95% CI 1.23 to 1.65), 22% (95% CI 1.07 to 1.40), and 10% (95% CI 0.98 to 1.22) greater risk for HF, CHD, and mortality, respectively. Associations seemed stronger for participants with CKD; however, no significant interactions were detected. Resting electrocardiographic abnormalities are common in CKD and independently predict future clinical CV events in this setting.
10aAged10aAged, 80 and over10aCardiac Output, Low10aCardiovascular Diseases10aChronic Disease10aCoronary Disease10aElectrocardiography10aFemale10aHumans10aKidney10aKidney Diseases10aMale10aRisk Assessment1 aKestenbaum, Bryan1 aRudser, Kyle, D1 aShlipak, Michael, G1 aFried, Linda, F1 aNewman, Anne, B1 aKatz, Ronit1 aSarnak, Mark, J1 aSeliger, Stephen1 aStehman-Breen, Catherine1 aPrineas, Ronald1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/97502911nas a2200397 4500008004100000022001400041245020400055210006900259260001600328300001100344490000800355520168900363653000902052653002202061653002102083653003102104653001902135653001102154653002202165653001102187653001402198653003002212653001102242653000902253653002402262653001702286653002102303653002002324100002502344700002102369700002002390700002402410700002202434700002102456856003602477 2008 eng d a1524-453900aAbdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.0 aAbdominal aortic aneurysms increasing infrarenal aortic diameter c2008 Feb 26 a1010-70 v1173 aBACKGROUND: Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse.
METHODS AND RESULTS: In 1992 to 1993, 4734 Cardiovascular Health Study participants > or = 65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter > or = 3.0 cm or an infrarenal/suprarenal ratio > or = 1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation > or = 3 cm identified 68% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4% of the total population and that a > or = 2.5-cm dilation identified 91% of all AAA repairs and 9 of the 10 deaths in 10% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95% confidence interval 1.25 to 1.85). Compared with diameters < 2.0 cm, infrarenal aortic diameters 2.0 to < 3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men.
CONCLUSIONS: This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters > 2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.
10aAged10aAged, 80 and over10aAorta, Abdominal10aAortic Aneurysm, Abdominal10aCause of Death10aFemale10aFollow-Up Studies10aHumans10aIncidence10aIntermittent Claudication10aKidney10aMale10aProspective Studies10aRisk Factors10aSex Distribution10aUltrasonography1 aFreiberg, Matthew, S1 aArnold, Alice, M1 aNewman, Anne, B1 aEdwards, Matthew, S1 aKraemer, Kevin, L1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/101702997nas a2200409 4500008004100000022001400041245003400055210003300089260001600122300001100138490000800149520198900157653000902146653001002155653001502165653001502180653001502195653001402210653001102224653002202235653003102257653001102288653001102299653000902310100002002319700001602339700002002355700002102375700002202396700002102418700001702439700001902456700002002475700002402495710003202519856003602551 2008 eng d a0003-992600aCystatin C and aging success.0 aCystatin C and aging success c2008 Jan 28 a147-530 v1683 aBACKGROUND: To our knowledge, the effect of kidney function on successful aging has not been examined.
METHODS: We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged >or= 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.
RESULTS: A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m(2), respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).
CONCLUSION: A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.
10aAged10aAging10aBiomarkers10aCreatinine10aCystatin C10aCystatins10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney10aMale1 aSarnak, Mark, J1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aKestenbaum, Brian1 aSeliger, Stephen1 aRifkin, Dena1 aTracy, Russell1 aNewman, Anne, B1 aShlipak, Michael, G1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/101302916nas a2200349 4500008004100000022001400041245007000055210006900125260001600194300001100210490000800221520198600229653000902215653002802224653001502252653001402267653001102281653003102292653001102323653001102334653000902345653001402354100002002368700002402388700001602412700002002428700002102448700002102469700002002490700002002510856003602530 2008 eng d a1538-367900aRapid kidney function decline and mortality risk in older adults.0 aRapid kidney function decline and mortality risk in older adults c2008 Nov 10 a2212-80 v1683 aBACKGROUND: Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults.
METHODS: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR(creat)) and cystatin C (eGFR(cys)) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m(2) per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up.
RESULTS: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR(creat) and eGFR(cys) were 79 (23) mL/min/1.73 m(2) and 79 (19) mL/min/1.73 m(2), respectively. Individuals with rapid decline measured by eGFR(creat) (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR(cys) (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease.
CONCLUSION: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatins10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aMortality1 aRifkin, Dena, E1 aShlipak, Michael, G1 aKatz, Ronit1 aFried, Linda, F1 aSiscovick, David1 aChonchol, Michel1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/106203044nas a2200445 4500008004100000022001400041245009600055210006900151260001300220300001200233490000800245520184200253653001602095653000902111653002002120653002802140653001502168653001502183653001102198653003102209653001802240653001102258653001102269653002002280653001802300653002502318653000902343653001502352653002002367653001702387653001702404653001802421100002402439700001602463700002202479700002002501700002102521700002002542856003602562 2009 eng d a1879-148400aClinical and subclinical cardiovascular disease and kidney function decline in the elderly.0 aClinical and subclinical cardiovascular disease and kidney funct c2009 May a298-3030 v2043 aOBJECTIVE: Kidney function decline in elderly persons may be the result of microvascular atherosclerosis. As a proxy for the renovascular system, we evaluated the association of clinical and subclinical cardiovascular disease (CVD) with kidney function decline.
METHODS: This study included 4380 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >or=65 from 4 U.S. communities. Creatinine and cystatin C were measured at baseline, year 3, and year 7; eligible subjects had at least two measures. Creatinine-based estimated glomerular filtration rate (eGFR(creat)) was calculated using the MDRD equation. Rapid kidney function decline was defined as an annual eGFR loss >3 mL/min/1.73 m(2). Predictors of rapid kidney decline included prevalent and subclinical measures of CVD.
RESULTS: Mean decline in eGFR(creat) was 0.4+/-2.6/year; 714 (16%) had rapid progression. In multivariate models adjusted for demographics, cardiovascular risk factors, and inflammation, prevalent stroke (OR, 95% CI: 1.55, 1.16-2.08) and heart failure (OR, 95% CI: 1.80, 1.40-2.31) were independent predictors of rapid kidney decline. Among persons without clinical CV, the subclinical disease measures ankle-arm index <0.9 (OR, 95% CI: 1.67, 1.25-2.24), common carotid intima-media thickness (>or=1.14 mm) (OR, 95% CI: 1.52, 1.12-2.06) and internal carotid intima-media thickness (>1.82 mm) (OR, 95% CI: 1.50, 1.12-2.02) had independent associations with rapid kidney function decline. Results were similar using cystatin C.
CONCLUSION: Clinical atherosclerosis and heart failure and subclinical measures of CVD have independent associations with kidney function decline progression in the elderly, suggesting an underlying role of renal atherosclerosis.
10aAge Factors10aAged10aAtherosclerosis10aCardiovascular Diseases10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aKidney10aKidney Diseases10aLinear Models10aLongitudinal Studies10aMale10aOdds Ratio10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aSiscovick, David1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/105703209nas a2200769 4500008004100000022001400041245008800055210006900143260001300212300001000225490000700235520104200242653002301284653001901307653002201326653003401348653003101382653001101413653001101424653002801435653002701463653001701490653001601507653003601523653001501559653001501574100001901589700002201608700001901630700002001649700001601669700001201685700001601697700002401713700002201737700002201759700002101781700001901802700001901821700002101840700002001861700002001881700002301901700002201924700002001946700002301966700001901989700001702008700002102025700002402046700001702070700002102087700002402108700001902132700002602151700002802177700002302205700002302228700002102251700002002272700002002292700002802312700001802340700002402358700002102382856003602403 2009 eng d a1546-171800aMultiple loci associated with indices of renal function and chronic kidney disease.0 aMultiple loci associated with indices of renal function and chro c2009 Jun a712-70 v413 aChronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 × 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein, and rare mutations in UMOD cause mendelian forms of kidney disease. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.
10aChromosome Mapping10aCohort Studies10aGenetic Variation10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aMeta-Analysis as Topic10aMucoproteins10aNetherlands10aPolymorphism, Single Nucleotide10aPrevalence10aUromodulin1 aKöttgen, Anna1 aGlazer, Nicole, L1 aDehghan, Abbas1 aHwang, Shih-Jen1 aKatz, Ronit1 aLi, Man1 aYang, Qiong1 aGudnason, Vilmundur1 aLauner, Lenore, J1 aHarris, Tamara, B1 aSmith, Albert, V1 aArking, Dan, E1 aAstor, Brad, C1 aBoerwinkle, Eric1 aEhret, Georg, B1 aRuczinski, Ingo1 aScharpf, Robert, B1 aChen, Yii-Der Ida1 ade Boer, Ian, H1 aHaritunians, Talin1 aLumley, Thomas1 aSarnak, Mark1 aSiscovick, David1 aBenjamin, Emelia, J1 aLevy, Daniel1 aUpadhyay, Ashish1 aAulchenko, Yurii, S1 aHofman, Albert1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aDuijn, Cornelia, M1 aChasman, Daniel, I1 aParé, Guillaume1 aRidker, Paul, M1 aKao, Linda, W H1 aWitteman, Jacqueline, C1 aCoresh, Josef1 aShlipak, Michael, G1 aFox, Caroline, S uhttps://chs-nhlbi.org/node/109903050nas a2200445 4500008004100000022001400041245006000055210005900115260001300174300001200187490000700199520190000206653000902106653001002115653002102125653002002146653002002166653001902186653001502205653001502220653001102235653003102246653001102277653001102288653002002299653002502319653000902344653001202353653001702365100002002382700001602402700002002418700001902438700002102457700002002478700002402498700002402522700002202546856003602568 2009 eng d a1523-683800aObesity and change in estimated GFR among older adults.0 aObesity and change in estimated GFR among older adults c2009 Dec a1043-510 v543 aBACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.
PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.
OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.
MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.
RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95% CI, 1.16-1.36) per 12 cm, and 1.14 (95% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.
LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.
CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.
10aAged10aAging10aBody Composition10aBody Mass Index10aChronic Disease10aCohort Studies10aCreatinine10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLongitudinal Studies10aMale10aObesity10aRisk Factors1 ade Boer, Ian, H1 aKatz, Ronit1 aFried, Linda, F1 aIx, Joachim, H1 aLuchsinger, Jose1 aSarnak, Mark, J1 aShlipak, Michael, G1 aSiscovick, David, S1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/113102550nas a2200373 4500008004100000022001400041245009900055210006900154260000900223300001000232490000700242520153600249653001601785653000901801653001501810653001501825653002401840653001101864653003101875653001101906653001101917653002001928653000901948653001701957100002401974700001601998700002202014700002002036700002002056700002402076700002002100700002002120856003602140 2009 eng d a1421-967000aRate of kidney function decline in older adults: a comparison using creatinine and cystatin C.0 aRate of kidney function decline in older adults a comparison usi c2009 a171-80 v303 aBACKGROUND/AIMS: The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
METHODS: In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 +/- 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m(2)).
RESULTS: Mean annual eGFR loss as estimated from creatinine was 0.4 +/- 3.6 ml/min/1.73 m(2), with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 +/- 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16-1.65), 1.62 (1.31-1.99) and 2.96 (2.28-3.84) for participants aged 70-74, 75-79 and 80+ at baseline, compared with those aged 65-69.
CONCLUSION: In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
10aAge Factors10aAged10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aRisk Factors1 aShlipak, Michael, G1 aKatz, Ronit1 aKestenbaum, Bryan1 aFried, Linda, F1 aNewman, Anne, B1 aSiscovick, David, S1 aStevens, Lesley1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/108902733nas a2200385 4500008004100000022001400041245006500055210006300120260001300183300001000196490000700206520170400213653001001917653000901927653002201936653002801958653001501986653001102001653001102012653001602023653002102039100002302060700001802083700002302101700002502124700001602149700002002165700002002185700002202205700001902227700002002246700002102266700002402287856003602311 2010 eng d a1460-238500aAge and cystatin C in healthy adults: a collaborative study.0 aAge and cystatin C in healthy adults a collaborative study c2010 Feb a463-90 v253 aBACKGROUND: Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum.
METHODS: The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.
RESULTS: Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).
CONCLUSIONS: There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.
10aAdult10aAged10aAged, 80 and over10aCross-Sectional Studies10aCystatin C10aHumans10aKidney10aMiddle Aged10aReference Values1 aOdden, Michelle, C1 aTager, Ira, B1 aGansevoort, Ron, T1 aBakker, Stephan, J L1 aKatz, Ronit1 aFried, Linda, F1 aNewman, Anne, B1 aCanada, Robert, B1 aHarris, Tamara1 aSarnak, Mark, J1 aSiscovick, David1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/112802802nas a2200373 4500008004100000022001400041245009600055210006900151260001300220300001100233490000700244520178400251653000902035653001002044653002102054653001902075653001502094653001102109653003102120653001102151653001102162653002002173653000902193653002402202100001902226700001602245700002102261700002202282700002002304700002402324700002002348700002402368856003602392 2010 eng d a1460-238500aAlcohol consumption and kidney function decline in the elderly: alcohol and kidney disease.0 aAlcohol consumption and kidney function decline in the elderly a c2010 Oct a3301-70 v253 aBACKGROUND: Alcohol consumption appears to be protective for cardiovascular disease; however, its relationship with kidney disease is unclear.
METHODS: This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged ≥65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, <1 drink, 1-6 drinks, 7-13 drinks and ≥14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFR(cys) was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFR(cys)) loss >3 mL/min/1.73 m(2)/year.
RESULTS: Eight percent of the cohort reported former alcohol use and 52% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95% confidence interval: none = reference; former = 1.18, 0.89-1.56; <1 drink = 1.20, 0.99-1.47; 1-6 = 1.18, 0.95-1.45; 7-13 = 1.10, 0.80-1.53; >14 = 0.89, 0.61-1.13). Results were similar with kidney function decline as a continuous outcome.
CONCLUSIONS: Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease.
10aAged10aAging10aAlcohol Drinking10aCohort Studies10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aProspective Studies1 aMenon, Vandana1 aKatz, Ronit1 aMukamal, Kenneth1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aSiscovick, David, S1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/118604123nas a2200817 4500008004100000022001400041245007500055210006900130260001300199300001200212490000700224520182200231653001002053653000902063653004002072653001102112653003002123653001902153653001702172653002202189653003402211653001102245653001102256653000902267653001602276653001502292653003602307653003102343653001602374653005402390100002202444700002202466700001902488700002102507700002002528700001702548700001702565700002802582700002402610700002602634700002202660700002002682700002202702700001802724700002302742700002002765700002202785700001602807700002002823700002002843700002102863700002202884700001202906700001902918700002102937700001802958700001602976700001702992700002603009700001903035700002603054700002803080700001903108700002303127700002403150700002003174700003003194700002403224700002103248856003603269 2010 eng d a1533-345000aCommon genetic variants associate with serum phosphorus concentration.0 aCommon genetic variants associate with serum phosphorus concentr c2010 Jul a1223-320 v213 aPhosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.
10aAdult10aAged10aEuropean Continental Ancestry Group10aFemale10aFibroblast Growth Factors10aGene Frequency10aGenetic Loci10aGenetic Variation10aGenome-Wide Association Study10aHumans10aKidney10aMale10aMiddle Aged10aPhosphorus10aPolymorphism, Single Nucleotide10aReceptors, Calcium-Sensing10aSex Factors10aSodium-Phosphate Cotransporter Proteins, Type IIa1 aKestenbaum, Bryan1 aGlazer, Nicole, L1 aKöttgen, Anna1 aFelix, Janine, F1 aHwang, Shih-Jen1 aLiu, Yongmei1 aLohman, Kurt1 aKritchevsky, Stephen, B1 aHausman, Dorothy, B1 aPetersen, Ann-Kristin1 aGieger, Christian1 aRied, Janina, S1 aMeitinger, Thomas1 aStrom, Tim, M1 aWichmann, Erich, H1 aCampbell, Harry1 aHayward, Caroline1 aRudan, Igor1 ade Boer, Ian, H1 aPsaty, Bruce, M1 aRice, Kenneth, M1 aChen, Yii-Der Ida1 aLi, Man1 aArking, Dan, E1 aBoerwinkle, Eric1 aCoresh, Josef1 aYang, Qiong1 aLevy, Daniel1 avan Rooij, Frank, J A1 aDehghan, Abbas1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aHofman, Albert1 aDuijn, Cornelia, M1 aShlipak, Michael, G1 aKao, Linda, W H1 aWitteman, Jacqueline, C M1 aSiscovick, David, S1 aFox, Caroline, S uhttps://chs-nhlbi.org/node/120603047nas a2200433 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520184200263653000902105653001502114653002302129653001902152653001502171653001102186653003102197653001102228653001702239653003802256653001802294653001102312653002002323653002502343653000902368653002402377653001802401100002402419700001602443700002002459700002002479700002202499700001802521700002402539710001402563856003602577 2010 eng d a1460-238500aInflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.0 aInflammatory biomarkers and decline in kidney function in the el c2010 Jan a119-240 v253 aBACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline.
METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin.
RESULTS: During the study, 1059 subjects (26%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen.
CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR.
10aAged10aBiomarkers10aC-Reactive Protein10aCohort Studies10aCystatin C10aFemale10aGlomerular Filtration Rate10aHumans10aInflammation10aIntercellular Adhesion Molecule-110aInterleukin-610aKidney10aLogistic Models10aLongitudinal Studies10aMale10aProspective Studies10aSerum Albumin1 aKeller, Christopher1 aKatz, Ronit1 aSarnak, Mark, J1 aFried, Linda, F1 aKestenbaum, Bryan1 aCushman, Mary1 aShlipak, Michael, G1 aCHS study uhttps://chs-nhlbi.org/node/112706326nas a2201873 4500008004100000022001400041245007300055210006900128260001300197300001100210490000700221520118400228653001901412653001501431653001501446653000901461653001101470653002001481653003401501653003101535653001101566653001101577653002801588653002001616653001701636100001901653700002201672700002301694700002701717700002001744700002201764700001801786700001601804700001601820700002101836700002601857700001201883700002001895700002001915700001801935700002001953700002001973700002301993700001902016700002202035700002102057700002702078700001802105700001702123700002502140700002902165700002402194700001802218700002202236700001902258700002402277700002202301700002202323700002402345700002502369700001902394700002102413700002302434700002602457700002202483700002602505700002002531700002002551700002302571700001902594700002102613700002002634700002502654700001902679700001802698700002202716700002302738700002302761700002002784700002102804700002102825700002402846700001802870700002202888700002202910700001802932700001802950700002302968700002202991700002103013700001603034700002203050700001803072700002103090700001703111700001903128700001603147700001903163700001903182700002003201700002003221700002203241700002203263700002403285700002103309700002603330700002803356700001903384700001903403700002103422700002503443700002303468700002203491700001803513700002203531700001803553700001803571700002003589700002203609700001903631700002103650700002003671700001703691700001903708700002203727700001903749700002503768700002003793700002403813700002403837700001703861700002003878700001803898700002003916700002403936700002103960700001403981700002403995700002304019700001804042700002204060700002004082700002404102700002304126700002004149700002504169700001604194700002004210700002104230700002804251700002604279700001904305700001704324700002304341700001304364700001804377700002104395856003604416 2010 eng d a1546-171800aNew loci associated with kidney function and chronic kidney disease.0 aNew loci associated with kidney function and chronic kidney dise c2010 May a376-840 v423 aChronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
10aCohort Studies10aCreatinine10aCystatin C10aDiet10aEurope10aGenetic Markers10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aModels, Genetic10aRisk Factors1 aKöttgen, Anna1 aPattaro, Cristian1 aBöger, Carsten, A1 aFuchsberger, Christian1 aOlden, Matthias1 aGlazer, Nicole, L1 aParsa, Afshin1 aGao, Xiaoyi1 aYang, Qiong1 aSmith, Albert, V1 aO'Connell, Jeffrey, R1 aLi, Man1 aSchmidt, Helena1 aTanaka, Toshiko1 aIsaacs, Aaron1 aKetkar, Shamika1 aHwang, Shih-Jen1 aJohnson, Andrew, D1 aDehghan, Abbas1 aTeumer, Alexander1 aParé, Guillaume1 aAtkinson, Elizabeth, J1 aZeller, Tanja1 aLohman, Kurt1 aCornelis, Marilyn, C1 aProbst-Hensch, Nicole, M1 aKronenberg, Florian1 aTönjes, Anke1 aHayward, Caroline1 aAspelund, Thor1 aEiriksdottir, Gudny1 aLauner, Lenore, J1 aHarris, Tamara, B1 aRampersaud, Evadnie1 aMitchell, Braxton, D1 aArking, Dan, E1 aBoerwinkle, Eric1 aStruchalin, Maksim1 aCavalieri, Margherita1 aSingleton, Andrew1 aGiallauria, Francesco1 aMetter, Jeffrey1 ade Boer, Ian, H1 aHaritunians, Talin1 aLumley, Thomas1 aSiscovick, David1 aPsaty, Bruce, M1 aZillikens, Carola, M1 aOostra, Ben, A1 aFeitosa, Mary1 aProvince, Michael1 ade Andrade, Mariza1 aTurner, Stephen, T1 aSchillert, Arne1 aZiegler, Andreas1 aWild, Philipp, S1 aSchnabel, Renate, B1 aWilde, Sandra1 aMunzel, Thomas, F1 aLeak, Tennille, S1 aIllig, Thomas1 aKlopp, Norman1 aMeisinger, Christa1 aWichmann, H-Erich1 aKoenig, Wolfgang1 aZgaga, Lina1 aZemunik, Tatijana1 aKolcic, Ivana1 aMinelli, Cosetta1 aHu, Frank, B1 aJohansson, Asa1 aIgl, Wilmar1 aZaboli, Ghazal1 aWild, Sarah, H1 aWright, Alan, F1 aCampbell, Harry1 aEllinghaus, David1 aSchreiber, Stefan1 aAulchenko, Yurii, S1 aFelix, Janine, F1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aHofman, Albert1 aImboden, Medea1 aNitsch, Dorothea1 aBrandstätter, Anita1 aKollerits, Barbara1 aKedenko, Lyudmyla1 aMägi, Reedik1 aStumvoll, Michael1 aKovacs, Peter1 aBoban, Mladen1 aCampbell, Susan1 aEndlich, Karlhans1 aVölzke, Henry1 aKroemer, Heyo, K1 aNauck, Matthias1 aVölker, Uwe1 aPolasek, Ozren1 aVitart, Veronique1 aBadola, Sunita1 aParker, Alexander, N1 aRidker, Paul, M1 aKardia, Sharon, L R1 aBlankenberg, Stefan1 aLiu, Yongmei1 aCurhan, Gary, C1 aFranke, Andre1 aRochat, Thierry1 aPaulweber, Bernhard1 aProkopenko, Inga1 aWang, Wei1 aGudnason, Vilmundur1 aShuldiner, Alan, R1 aCoresh, Josef1 aSchmidt, Reinhold1 aFerrucci, Luigi1 aShlipak, Michael, G1 aDuijn, Cornelia, M1 aBorecki, Ingrid1 aKrämer, Bernhard, K1 aRudan, Igor1 aGyllensten, Ulf1 aWilson, James, F1 aWitteman, Jacqueline, C1 aPramstaller, Peter, P1 aRettig, Rainer1 aHastie, Nick1 aChasman, Daniel, I1 aKao, W H1 aHeid, Iris, M1 aFox, Caroline, S uhttps://chs-nhlbi.org/node/118302817nas a2200385 4500008004100000022001400041245012300055210006900178260000900247300001500256490000600271520169500277653000901972653002801981653001502009653003702024653001102061653003102072653001102103653001702114653001102131653002502142653000902167653002402176100002302200700001802223700002602241700002502267700002302292700001602315700002002331700002002351700002402371856003602395 2011 eng d a1557-467900aAntihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis.0 aAntihypertensive medication use and change in kidney function in c2011 aArticle 340 v73 aBACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.
METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.
RESULTS: The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.
CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.
10aAged10aAntihypertensive Agents10aCystatin C10aData Interpretation, Statistical10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aKidney10aLongitudinal Studies10aMale10aModels, Statistical1 aOdden, Michelle, C1 aTager, Ira, B1 avan der Laan, Mark, J1 aDelaney, Joseph, A C1 aPeralta, Carmen, A1 aKatz, Ronit1 aSarnak, Mark, J1 aPsaty, Bruce, M1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/134803030nas a2200505 4500008004100000022001400041245004500055210004400100260001300144300001100157490000600168520171200174653001601886653002201902653002501924653001501949653002801964653002801992653002002020653001502040653002802055653001502083653002202098653001102120653003102131653001102162653001102173653002002184653002002204653000902224653002302233653001502256653002002271653001702291653001802308100001902326700002302345700001602368700002002384700002002404700002402424700002002448700002002468856003602488 2011 eng d a1555-905X00aChronic kidney disease in octogenarians.0 aChronic kidney disease in octogenarians c2011 Jun a1410-70 v63 aBACKGROUND AND OBJECTIVES: There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.
RESULTS: Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95% CI, 1.55, 2.83).
CONCLUSIONS: Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.
10aAge Factors10aAged, 80 and over10aAnalysis of Variance10aBiomarkers10aCardiovascular Diseases10aChi-Square Distribution10aChronic Disease10aCreatinine10aCross-Sectional Studies10aCystatin C10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aLogistic Models10aMale10aModels, Biological10aPrevalence10aRisk Assessment10aRisk Factors10aUnited States1 aShastri, Shani1 aTighiouart, Hocine1 aKatz, Ronit1 aRifkin, Dena, E1 aFried, Linda, F1 aShlipak, Michael, G1 aNewman, Anne, B1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/128604453nas a2200889 4500008004100000022001400041245011700055210006900172260001300241300001300254490000600267520190600273653004202179653001002221653003902231653000902270653001202279653001102291653003002302653003202332653001702364653003402381653003102415653001102446653002802457653001102485653002802496653000902524653001602533653002202549653001402571653003602585653001402621100001802635700002202653700001802675700001902693700002302712700002302735700002002758700001702778700002402795700002002819700001902839700002002858700001802878700002102896700002902917700002102946700002202967700001802989700001603007700002303023700001203046700002403058700002503082700002303107700002303130700002303153700002303176700002203199700002203221700002303243700001703266700002403283700002203307700002403329700001803353700002503371700002503396700002303421700002503444700001503469700002103484710002203505856003603527 2011 eng d a1553-740400aGenetic association for renal traits among participants of African ancestry reveals new loci for renal function.0 aGenetic association for renal traits among participants of Afric c2011 Sep ae10022640 v73 aChronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m(2)), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7)) and FNDC1 (p-value = 3.0×10(-7)) for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6)). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.
10aAdaptor Proteins, Vesicular Transport10aAdult10aAfrican Continental Ancestry Group10aAged10aAnimals10aFemale10aGene Knockdown Techniques10aGenetic Association Studies10aGenetic Loci10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKCNQ1 Potassium Channel10aKidney10aKidney Failure, Chronic10aMale10aMiddle Aged10aNeoplasm Proteins10aPhenotype10aPolymorphism, Single Nucleotide10aZebrafish1 aLiu, Ching-Ti1 aGarnaas, Maija, K1 aTin, Adrienne1 aKöttgen, Anna1 aFranceschini, Nora1 aPeralta, Carmen, A1 ade Boer, Ian, H1 aLu, Xiaoning1 aAtkinson, Elizabeth1 aDing, Jingzhong1 aNalls, Michael1 aShriner, Daniel1 aCoresh, Josef1 aKutlar, Abdullah1 aBibbins-Domingo, Kirsten1 aSiscovick, David1 aAkylbekova, Ermeg1 aWyatt, Sharon1 aAstor, Brad1 aMychaleckjy, Josef1 aLi, Man1 aReilly, Muredach, P1 aTownsend, Raymond, R1 aAdeyemo, Adebowale1 aZonderman, Alan, B1 ade Andrade, Mariza1 aTurner, Stephen, T1 aMosley, Thomas, H1 aHarris, Tamara, B1 aRotimi, Charles, N1 aLiu, Yongmei1 aKardia, Sharon, L R1 aEvans, Michele, K1 aShlipak, Michael, G1 aKramer, Holly1 aFlessner, Michael, F1 aDreisbach, Albert, W1 aGoessling, Wolfram1 aCupples, Adrienne, L1 aKao, Linda1 aFox, Caroline, S1 aCKDGen Consortium uhttps://chs-nhlbi.org/node/132702802nas a2200469 4500008004100000022001400041245009700055210006900152260000900221300001000230490000700240520155000247653000901797653002801806653001501834653001501849653002401864653001101888653001501899653003101914653001101945653001101956653002001967653000901987653001601996653002202012653001702034653002202051100002302073700001602096700002102112700001602133700001602149700001702165700002502182700001602207700002202223700001602245700001702261700001802278856003602296 2011 eng d a1421-967000aKidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2).0 aKidney function decline in the elderly impact of lipoproteinasso c2011 a512-80 v343 aBACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied.
METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m(2)).
RESULTS: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline.
CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.
10aAged10aCardiovascular Diseases10aCreatinine10aCystatin C10aDisease Progression10aFemale10aGeriatrics10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Diseases10aMale10aMiddle Aged10aPhospholipases A210aRisk Factors10aTreatment Outcome1 aPeralta, Carmen, A1 aKatz, Ronit1 aShlipak, Michael1 aDubin, Ruth1 aDeBoer, Ian1 aJenny, Nancy1 aFitzpatrick, Annette1 aKoro, Carol1 aKestenbaum, Bryan1 aIx, Joachim1 aSarnak, Mark1 aCushman, Mary uhttps://chs-nhlbi.org/node/134903030nas a2200517 4500008004100000022001400041245010800055210006900163260001300232300001100245490000700256520161100263653000901874653002801883653001601911653002701927653002201954653001101976653002201987653001102009653001702020653001402037653001102051653000902062653001602071653001302087653002402100653003202124653001702156653002602173653001802199653001402217100001502231700001602246700002402262700002202286700002002308700002002328700002002348700002102368700002002389700002402409700002102433700002202454856003602476 2011 eng d a1524-456300aVitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.0 aVitamin D parathyroid hormone and sudden cardiac death results f c2011 Dec a1021-80 v583 aRecent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.
10aAged10aCardiovascular Diseases10aComorbidity10aDeath, Sudden, Cardiac10aDiabetes Mellitus10aFemale10aFollow-Up Studies10aHumans10aHypertension10aIncidence10aKidney10aMale10aMiddle Aged10aMinerals10aParathyroid Hormone10aProportional Hazards Models10aRisk Factors10aSocioeconomic Factors10aUnited States10aVitamin D1 aDeo, Rajat1 aKatz, Ronit1 aShlipak, Michael, G1 aSotoodehnia, Nona1 aPsaty, Bruce, M1 aSarnak, Mark, J1 aFried, Linda, F1 aChonchol, Michel1 ade Boer, Ian, H1 aEnquobahrie, Daniel1 aSiscovick, David1 aKestenbaum, Bryan uhttps://chs-nhlbi.org/node/135004194nas a2200517 4500008004100000022001400041245008700055210006900142260001600211300001200227490000800239520279100247653001503038653001003053653001603063653000903079653001603088653001903104653001103123653003103134653001103165653001103176653002803187653000903215653001603224653000903240653001603249100002103265700002503286700001903311700002703330700001703357700001803374700002103392700001903413700001903432700002203451700002303473700001903496700002303515700001803538700001803556700001803574710004803592856003603640 2012 eng d a1538-359800aAge and association of kidney measures with mortality and end-stage renal disease.0 aAge and association of kidney measures with mortality and endsta c2012 Dec 12 a2349-600 v3083 aCONTEXT: Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial.
OBJECTIVE: To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks.
DESIGN, SETTING, AND PARTICIPANTS: Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years).
MAIN OUTCOME MEASURES: Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates.
RESULTS: Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories.
CONCLUSIONS: Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.
10aAdolescent10aAdult10aAge Factors10aAged10aAlbuminuria10aCohort Studies10aFemale10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aMale10aMiddle Aged10aRisk10aYoung Adult1 aHallan, Stein, I1 aMatsushita, Kunihiro1 aSang, Yingying1 aMahmoodi, Bakhtawar, K1 aBlack, Corri1 aIshani, Areef1 aKleefstra, Nanne1 aNaimark, David1 aRoderick, Paul1 aTonelli, Marcello1 aWetzels, Jack, F M1 aAstor, Brad, C1 aGansevoort, Ron, T1 aLevin, Adeera1 aWen, Chi-Pang1 aCoresh, Josef1 aChronic Kidney Disease Prognosis Consortium uhttps://chs-nhlbi.org/node/738002904nas a2200457 4500008004100000022001400041245005800055210005700113260001300170300001100183490000700194520167600201653000901877653002201886653001201908653002201920653002501942653001501967653002801982653001502010653002402025653004002049653001102089653001902100653001302119653003102132653001102163653001102174653000902185653001502194653003302209653001702242100003002259700001602289700002002305700002102325700002402346700002002370700002002390856003602410 2012 eng d a0301-043000aApolipoprotein E and kidney function in older adults.0 aApolipoprotein E and kidney function in older adults c2012 Sep a174-800 v783 aBACKGROUND: Previous studies suggest that the ε4 and ε2 alleles of apolipoprotein E (APOE) may be associated with decreased and increased risks of CKD, respectively, but there are limited data in older adults. We evaluated the associations of apolipoprotein E alleles with kidney function among older adults in the cardiovascular health study (CHS).
METHODS: Caucasian participants had APOE allelic analysis and serum creatinine and cystatin C measured at baseline (n = 3,844 for cross sectional analysis) and in follow up (n = 3,226 for longitudinal analysis). APOE variation was evaluated as an additive model with number of ε2, ε3 and ε4 alleles. GFR was estimated using the CKD epidemiology equation (eGFRcreat) and the cystatin C demographic equation (eGFRcys). The primary outcome was CKD defined by eGFR < 60 ml/min/1.73 m2. The secondary outcome was rapid progression defined by annual loss of eGFR > 3 ml/min/1.73 m2.
RESULTS: Mean eGFRcreat was 72 ml/min/1.73 m2 (25% CKD). Compared with the ε3 allele, the APOE ε4 allele was associated with reduced risk of CKD by eGFRcreat: unadjusted odds ratio (OR) and 95% confidence interval (CI) 0.79 (0.67 - 0.93) per allele, fully adjusted OR (95% CI) 0.80 (0.68 - 0.96) per allele. Results were consistent using eGFRcys. There was no association of the ε2 allele with CKD or between the apolipoprotein E gene with rapid progression.
CONCLUSIONS: The apolipoprotein ε4 allele was associated with lower odds of CKD in elderly Caucasian individuals. Future research should confirm these findings in other races and explore mechanisms to explain these results.
10aAged10aAged, 80 and over10aAlleles10aApolipoproteins E10aConfidence Intervals10aCreatinine10aCross-Sectional Studies10aCystatin C10aDisease Progression10aEuropean Continental Ancestry Group10aFemale10aGene Frequency10aGenotype10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aOdds Ratio10aRenal Insufficiency, Chronic10aRisk Factors1 aSeshasai, Rebecca, Kurnik1 aKatz, Ronit1 ade Boer, Ian, H1 aSiscovick, David1 aShlipak, Michael, G1 aRifkin, Dena, E1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/586203276nas a2200541 4500008004100000022001400041245008700055210006900142260001300211300001100224490000600235520180000241653001602041653000902057653002202066653001502088653002002103653001502123653002202138653001102160653003102171653002702202653001902229653001102248653002402259653001402283653001202297653002302309653002802332653001102360653002002371653001802391653000902409653003202418653002002450653001702470653001802487100001502505700003002520700001902550700001902569700002402588700002002612700002202632700002402654700002002678856003602698 2012 eng d a1555-905X00aChronic kidney disease, insulin resistance, and incident diabetes in older adults.0 aChronic kidney disease insulin resistance and incident diabetes c2012 Apr a588-940 v73 aBACKGROUND AND OBJECTIVES: Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic β cell, effects on glucose tolerance, and risk of diabetes are not clear.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, β cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose ≥126 mg/dl, nonfasting glucose ≥200 mg/dl, or use of glucose-lowering medications.
RESULTS: Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2% higher fasting insulin concentration (95% confidence interval [CI], 1.4%, 2.9%; P<0.001) and a 1.1% lower insulin sensitivity index (95% CI, 0.03%, 2.2%; P=0.04). Surprisingly, eGFR was associated with an augmented β cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years' follow-up, 437 participants (9.3%) developed diabetes. eGFR was not associated with the risk of incident diabetes.
CONCLUSIONS: Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased.
10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aChronic Disease10aCreatinine10aDiabetes Mellitus10aFemale10aGlomerular Filtration Rate10aGlucose Tolerance Test10aHealth Surveys10aHumans10aHypoglycemic Agents10aIncidence10aInsulin10aInsulin Resistance10aInsulin-Secreting Cells10aKidney10aKidney Diseases10aLinear Models10aMale10aProportional Hazards Models10aRisk Assessment10aRisk Factors10aUnited States1 aPham, Hien1 aRobinson-Cohen, Cassianne1 aBiggs, Mary, L1 aIx, Joachim, H1 aMukamal, Kenneth, J1 aFried, Linda, F1 aKestenbaum, Bryan1 aSiscovick, David, S1 ade Boer, Ian, H uhttps://chs-nhlbi.org/node/136803412nas a2200541 4500008004100000022001400041245009900055210006900154260001300223300001200236490000700248520175400255653005002009653001202059653002202071653001902093653002202112653002302134653003002157653003802187653004002225653001102265653001102276653002002287653000902307653003602316653003002352653001602382653002802398653000902426653002202435653002102457653002202478653005202500653002702552653002902579653002402608100002102632700002302653700001802676700002502694700002302719700002102742700002502763700002202788700002402810856003602834 2012 eng d a1524-456300aGenetic variants in Arhgef11 are associated with kidney injury in the Dahl salt-sensitive rat.0 aGenetic variants in Arhgef11 are associated with kidney injury i c2012 Nov a1157-680 v603 aA previous genetic analysis comparing the Dahl salt-sensitive (S) rat with the spontaneously hypertensive rat identified a major locus on chromosome 2 that influences proteinuria in the S rat. In the present study, blood pressure, proteinuria, and renal hemodynamics were evaluated in congenic strains with small segments of the protective spontaneously hypertensive rat genome on the S background. Proteinuria and renal function were significantly improved in the congenic strains compared with the S. The causative locus interval was narrowed to <375 kb on the basis of congenic strains, haplotype data, comparative mapping, and concordance with human genetic studies. Sequencing of the coding region of genes in this region identified 36 single nucleotide polymorphisms (13 nonsynonymous and 23 synonymous). Gene expression profiling indicated that only a few genes exhibited differential expression. Arhgef11, Pear1, and Sh2d2 were identified as important candidate genes that may be linked to kidney injury in the S rat. In particular, Arhgef11 plays an important role in the activation of the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted in a significant reduction of proteinuria in treated S rats (compared with untreated S). However, no difference was observed between treated or untreated spontaneously hypertensive rat or congenic strains. The homologous region in humans was found to be associated with estimated glomerular filtration rate in the Candidate Gene Association Resource population. In summary, these findings demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK pathway, could influence kidney injury in the S as well as provide insight into human kidney disease.
10a1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine10aAnimals10aAnimals, Congenic10aBlood Pressure10aBlotting, Western10aChromosome Mapping10aGene Expression Profiling10aGenetic Predisposition to Disease10aGuanine Nucleotide Exchange Factors10aHumans10aKidney10aKidney Diseases10aMale10aPolymorphism, Single Nucleotide10aProtein Kinase Inhibitors10aProteinuria10aQuantitative Trait Loci10aRats10aRats, Inbred Dahl10aRats, Inbred SHR10aRenal Circulation10aReverse Transcriptase Polymerase Chain Reaction10arho-Associated Kinases10arhoA GTP-Binding Protein10aSignal Transduction1 aWilliams, Jan, M1 aJohnson, Ashley, C1 aStelloh, Cary1 aDreisbach, Albert, W1 aFranceschini, Nora1 aRegner, Kevin, R1 aTownsend, Raymond, R1 aRoman, Richard, J1 aGarrett, Michael, R uhttps://chs-nhlbi.org/node/609307422nas a2202413 4500008004100000022001400041245009100055210006900146260000900215300001300224490000600237520076400243653002201007653000901029653001201038653001401050653002901064653002701093653001801120653004001138653001101178653002201189653003001211653003401241653003101275653001101306653001101317653002801328653000901356653001601365653003401381653001401415100002201429700001901451700002201470700001901492700002301511700002701534700002001561700002001581700001801601700001901619700001201638700001601650700002001666700001601686700002501702700002401727700002601751700001901777700001801796700001801814700002101832700002601853700002301879700002001902700001201922700002301934700002201957700001801979700002001997700002702017700001702044700002502061700001902086700001802105700001902123700002202142700002702164700002102191700002102212700002202233700001602255700002202271700001802293700001902311700002102330700002002351700001902371700002302390700002002413700002202433700002202455700001902477700002402496700002502520700002102545700002002566700002602586700002002612700001702632700001902649700001902668700002302687700002302710700002002733700002502753700002302778700002102801700001802822700002002840700002202860700001802882700002202900700001802922700002102940700002402961700001602985700001903001700001903020700002003039700002003059700002203079700002003101700001903121700001903140700002203159700001903181700001803200700002103218700002003239700002003259700001703279700001903296700001803315700002203333700001803355700001903373700002803392700002603420700002403446700001903470700001703489700002203506700002203528700001903550700002203569700001903591700002003610700001903630700002203649700002203671700002003693700001903713700001603732700002303748700002303771700002503794700001803819700001403837700002403851700001703875700002103892700002403913700001703937700001703954700001903971700001903990700001904009700001904028700002404047700002004071700002104091700001804112700002104130700001904151700001904170700002904189700002404218700002104242700002404263700002304287700001804310700002204328700002004350700002404370700002304394700002004417700002404437700001704461700002004478700001604498700002004514700002104534700001804555700002604573700001904599700002104618700003004639700002204669700001704691700001804708700002104726700001804747700002304765700002304788700002004811700002104831710002604852710002004878710002004898710005404918856003604972 2012 eng d a1553-740400aGenome-wide association and functional follow-up reveals new loci for kidney function.0 aGenomewide association and functional followup reveals new loci c2012 ae10025840 v83 aChronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
10aAfrican Americans10aAged10aAnimals10aCaspase 910aCyclin-Dependent Kinases10aDEAD-box RNA Helicases10aDNA Helicases10aEuropean Continental Ancestry Group10aFemale10aFollow-Up Studies10aGene Knockdown Techniques10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aMale10aMiddle Aged10aPhosphoric Diester Hydrolases10aZebrafish1 aPattaro, Cristian1 aKöttgen, Anna1 aTeumer, Alexander1 aGarnaas, Maija1 aBöger, Carsten, A1 aFuchsberger, Christian1 aOlden, Matthias1 aChen, Ming-Huei1 aTin, Adrienne1 aTaliun, Daniel1 aLi, Man1 aGao, Xiaoyi1 aGorski, Mathias1 aYang, Qiong1 aHundertmark, Claudia1 aFoster, Meredith, C1 aO'Seaghdha, Conall, M1 aGlazer, Nicole1 aIsaacs, Aaron1 aLiu, Ching-Ti1 aSmith, Albert, V1 aO'Connell, Jeffrey, R1 aStruchalin, Maksim1 aTanaka, Toshiko1 aLi, Guo1 aJohnson, Andrew, D1 aGierman, Hinco, J1 aFeitosa, Mary1 aHwang, Shih-Jen1 aAtkinson, Elizabeth, J1 aLohman, Kurt1 aCornelis, Marilyn, C1 aJohansson, Asa1 aTönjes, Anke1 aDehghan, Abbas1 aChouraki, Vincent1 aHolliday, Elizabeth, G1 aSorice, Rossella1 aKutalik, Zoltán1 aLehtimäki, Terho1 aEsko, Tõnu1 aDeshmukh, Harshal1 aUlivi, Sheila1 aChu, Audrey, Y1 aMurgia, Federico1 aTrompet, Stella1 aImboden, Medea1 aKollerits, Barbara1 aPistis, Giorgio1 aHarris, Tamara, B1 aLauner, Lenore, J1 aAspelund, Thor1 aEiriksdottir, Gudny1 aMitchell, Braxton, D1 aBoerwinkle, Eric1 aSchmidt, Helena1 aCavalieri, Margherita1 aRao, Madhumathi1 aHu, Frank, B1 aDemirkan, Ayse1 aOostra, Ben, A1 ade Andrade, Mariza1 aTurner, Stephen, T1 aDing, Jingzhong1 aAndrews, Jeanette, S1 aFreedman, Barry, I1 aKoenig, Wolfgang1 aIllig, Thomas1 aDöring, Angela1 aWichmann, H-Erich1 aKolcic, Ivana1 aZemunik, Tatijana1 aBoban, Mladen1 aMinelli, Cosetta1 aWheeler, Heather, E1 aIgl, Wilmar1 aZaboli, Ghazal1 aWild, Sarah, H1 aWright, Alan, F1 aCampbell, Harry1 aEllinghaus, David1 aNöthlings, Ute1 aJacobs, Gunnar1 aBiffar, Reiner1 aEndlich, Karlhans1 aErnst, Florian1 aHomuth, Georg1 aKroemer, Heyo, K1 aNauck, Matthias1 aStracke, Sylvia1 aVölker, Uwe1 aVölzke, Henry1 aKovacs, Peter1 aStumvoll, Michael1 aMägi, Reedik1 aHofman, Albert1 aUitterlinden, André, G1 aRivadeneira, Fernando1 aAulchenko, Yurii, S1 aPolasek, Ozren1 aHastie, Nick1 aVitart, Veronique1 aHelmer, Catherine1 aWang, Jie, Jin1 aRuggiero, Daniela1 aBergmann, Sven1 aKähönen, Mika1 aViikari, Jorma1 aNikopensius, Tiit1 aProvince, Michael1 aKetkar, Shamika1 aColhoun, Helen1 aDoney, Alex1 aRobino, Antonietta1 aGiulianini, Franco1 aKrämer, Bernhard, K1 aPortas, Laura1 aFord, Ian1 aBuckley, Brendan, M1 aAdam, Martin1 aThun, Gian-Andri1 aPaulweber, Bernhard1 aHaun, Margot1 aSala, Cinzia1 aMetzger, Marie1 aMitchell, Paul1 aCiullo, Marina1 aKim, Stuart, K1 aVollenweider, Peter1 aRaitakari, Olli1 aMetspalu, Andres1 aPalmer, Colin1 aGasparini, Paolo1 aPirastu, Mario1 aJukema, Wouter1 aProbst-Hensch, Nicole, M1 aKronenberg, Florian1 aToniolo, Daniela1 aGudnason, Vilmundur1 aShuldiner, Alan, R1 aCoresh, Josef1 aSchmidt, Reinhold1 aFerrucci, Luigi1 aSiscovick, David, S1 aDuijn, Cornelia, M1 aBorecki, Ingrid1 aKardia, Sharon, L R1 aLiu, Yongmei1 aCurhan, Gary, C1 aRudan, Igor1 aGyllensten, Ulf1 aWilson, James, F1 aFranke, Andre1 aPramstaller, Peter, P1 aRettig, Rainer1 aProkopenko, Inga1 aWitteman, Jacqueline, C M1 aHayward, Caroline1 aRidker, Paul1 aParsa, Afshin1 aBochud, Murielle1 aHeid, Iris, M1 aGoessling, Wolfram1 aChasman, Daniel, I1 aKao, Linda, W H1 aFox, Caroline, S1 aCARDIoGRAM consortium1 aICBP Consortium1 aCARe Consortium1 aWellcome Trust Case Control Consortium 2 (WTCCC2) uhttps://chs-nhlbi.org/node/137702611nas a2200337 4500008004100000022001400041245008200055210006900137260001300206300001100219490000700230520170400237653000901941653001901950653001101969653003101980653002002011653001102031653001402042653001102056653000902067653001702076100002502093700001602118700002202134700002002156700001702176700002002193700002402213856003602237 2012 eng d a1523-683800aThe risk of infection-related hospitalization with decreased kidney function.0 arisk of infectionrelated hospitalization with decreased kidney f c2012 Mar a356-630 v593 aBACKGROUND: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.
STUDY DESIGN: Cohort study.
SETTING & PARTICIPANTS: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m(2) at enrollment.
PREDICTOR: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)).
OUTCOME: Infection-related hospitalizations during a median follow-up of 11.5 years.
RESULTS: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16%, 37%, and 64% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2). When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m(2) was associated with an 80% greater risk of pulmonary and 160% greater risk of genitourinary infection compared with eGFR(SCysC) ≥90 mL/min/1.73 m(2).
LIMITATIONS: No measures of urinary protein, study limited to principal discharge diagnosis.
CONCLUSIONS: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.
10aAged10aCohort Studies10aFemale10aGlomerular Filtration Rate10aHospitalization10aHumans10aInfection10aKidney10aMale10aRisk Factors1 aDalrymple, Lorien, S1 aKatz, Ronit1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aFried, Linda1 aSarnak, Mark, J1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/132207440nas a2202173 4500008004100000022001400041245009700055210006900152260001300221300001200234490000700246520143200253653002301685653004001708653001901748653002201767653003401789653001101823653001101834653003701845653001401882653003601896653003301932100001801965700002701983700001902010700002602029700002202055700002302077700002302100700002202123700002202145700002002167700002002187700001802207700001802225700001902243700001202262700001802274700002002292700001602312700002502328700002402353700001902377700001802396700002002414700002102434700002602455700002302481700002002504700001202524700002002536700002702556700001702583700002502600700001902625700001802644700001902662700002102681700002702702700002102729700002102750700002202771700001602793700002202809700001802831700001902849700002102868700002002889700001902909700002302928700002002951700002202971700002202993700001903015700002403034700002503058700002103083700002003104700001703124700001403141700001903155700001903174700002303193700002003216700002503236700002303261700002303284700002103307700001803328700002003346700002203366700001603388700002203404700001803426700002103444700002403465700001603489700001903505700001903524700002003543700002003563700002203583700002003605700001903625700001903644700001903663700001803682700002103700700002003721700002003741700001703761700001903778700001803797700002203815700001803837700001903855700002803874700002603902700002403928700001903952700001703971700002203988700002204010700001904032700002504051700002204076700001904098700002004117700001904137700002204156700002204178700001904200700001604219700002304235700002504258700001804283700001404301700002404315700001704339700002104356700002404377700001704401700001704418700001904435700001904454700002404473700002004497700002104517700001804538700002104556700001904577700001904596700002904615700002404644700002104668700002404689700002304713700001804736700002204754700002004776700002304796700002004819700002404839700001704863700002004880700001604900700002004916700002104936700001804957700002604975700001905001700002105020700002505041700002205066700002005088700002105108700001805129700002405147700002105171700001505192700002305207856003605230 2013 eng d a1533-345000aCommon variants in Mendelian kidney disease genes and their association with renal function.0 aCommon variants in Mendelian kidney disease genes and their asso c2013 Dec a2105-170 v243 aMany common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
10aDatabases, Genetic10aEuropean Continental Ancestry Group10aGene Frequency10aGenetic Variation10aGenome-Wide Association Study10aHumans10aKidney10aMendelian Randomization Analysis10aPhenotype10aPolymorphism, Single Nucleotide10aRenal Insufficiency, Chronic1 aParsa, Afshin1 aFuchsberger, Christian1 aKöttgen, Anna1 aO'Seaghdha, Conall, M1 aPattaro, Cristian1 ade Andrade, Mariza1 aChasman, Daniel, I1 aTeumer, Alexander1 aEndlich, Karlhans1 aOlden, Matthias1 aChen, Ming-Huei1 aTin, Adrienne1 aKim, Young, J1 aTaliun, Daniel1 aLi, Man1 aFeitosa, Mary1 aGorski, Mathias1 aYang, Qiong1 aHundertmark, Claudia1 aFoster, Meredith, C1 aGlazer, Nicole1 aIsaacs, Aaron1 aRao, Madhumathi1 aSmith, Albert, V1 aO'Connell, Jeffrey, R1 aStruchalin, Maksim1 aTanaka, Toshiko1 aLi, Guo1 aHwang, Shih-Jen1 aAtkinson, Elizabeth, J1 aLohman, Kurt1 aCornelis, Marilyn, C1 aJohansson, Asa1 aTönjes, Anke1 aDehghan, Abbas1 aCouraki, Vincent1 aHolliday, Elizabeth, G1 aSorice, Rossella1 aKutalik, Zoltán1 aLehtimäki, Terho1 aEsko, Tõnu1 aDeshmukh, Harshal1 aUlivi, Sheila1 aChu, Audrey, Y1 aMurgia, Federico1 aTrompet, Stella1 aImboden, Medea1 aKollerits, Barbara1 aPistis, Giorgio1 aHarris, Tamara, B1 aLauner, Lenore, J1 aAspelund, Thor1 aEiriksdottir, Gudny1 aMitchell, Braxton, D1 aBoerwinkle, Eric1 aSchmidt, Helena1 aHofer, Edith1 aHu, Frank1 aDemirkan, Ayse1 aOostra, Ben, A1 aTurner, Stephen, T1 aDing, Jingzhong1 aAndrews, Jeanette, S1 aFreedman, Barry, I1 aGiulianini, Franco1 aKoenig, Wolfgang1 aIllig, Thomas1 aDöring, Angela1 aWichmann, H-Erich1 aZgaga, Lina1 aZemunik, Tatijana1 aBoban, Mladen1 aMinelli, Cosetta1 aWheeler, Heather, E1 aIgl, Wilmar1 aZaboli, Ghazal1 aWild, Sarah, H1 aWright, Alan, F1 aCampbell, Harry1 aEllinghaus, David1 aNöthlings, Ute1 aJacobs, Gunnar1 aBiffar, Reiner1 aErnst, Florian1 aHomuth, Georg1 aKroemer, Heyo, K1 aNauck, Matthias1 aStracke, Sylvia1 aVölker, Uwe1 aVölzke, Henry1 aKovacs, Peter1 aStumvoll, Michael1 aMägi, Reedik1 aHofman, Albert1 aUitterlinden, André, G1 aRivadeneira, Fernando1 aAulchenko, Yurii, S1 aPolasek, Ozren1 aHastie, Nick1 aVitart, Veronique1 aHelmer, Catherine1 aWang, Jie, Jin1 aStengel, Bénédicte1 aRuggiero, Daniela1 aBergmann, Sven1 aKähönen, Mika1 aViikari, Jorma1 aNikopensius, Tiit1 aProvince, Michael1 aColhoun, Helen1 aDoney, Alex1 aRobino, Antonietta1 aKrämer, Bernhard, K1 aPortas, Laura1 aFord, Ian1 aBuckley, Brendan, M1 aAdam, Martin1 aThun, Gian-Andri1 aPaulweber, Bernhard1 aHaun, Margot1 aSala, Cinzia1 aMitchell, Paul1 aCiullo, Marina1 aVollenweider, Peter1 aRaitakari, Olli1 aMetspalu, Andres1 aPalmer, Colin1 aGasparini, Paolo1 aPirastu, Mario1 aJukema, Wouter1 aProbst-Hensch, Nicole, M1 aKronenberg, Florian1 aToniolo, Daniela1 aGudnason, Vilmundur1 aShuldiner, Alan, R1 aCoresh, Josef1 aSchmidt, Reinhold1 aFerrucci, Luigi1 aDuijn, Cornelia, M1 aBorecki, Ingrid1 aKardia, Sharon, L R1 aLiu, Yongmei1 aCurhan, Gary, C1 aRudan, Igor1 aGyllensten, Ulf1 aWilson, James, F1 aFranke, Andre1 aPramstaller, Peter, P1 aRettig, Rainer1 aProkopenko, Inga1 aWitteman, Jacqueline1 aHayward, Caroline1 aRidker, Paul, M1 aBochud, Murielle1 aHeid, Iris, M1 aSiscovick, David, S1 aFox, Caroline, S1 aKao, Linda1 aBöger, Carsten, A uhttps://chs-nhlbi.org/node/628803866nas a2200613 4500008004100000022001400041245005600055210005500111260001300166300001100179490000600190520229500196653001602491653000902507653002202516653001002538653001502548653001502563653002802578653001502606653001202621653001102633653001802644653002502662653003102687653001102718653001402729653002302743653001102766653002002777653002002797653000902817653001902826653002602845653002002871653001502891653001402906653001502920653002402935653001702959653001702976653001802993653001603011100002503027700001603052700002003068700002103088700002003109700002003129700002003149700002303169700002403192856003603216 2013 eng d a1555-905X00aKidney function and prevalent and incident frailty.0 aKidney function and prevalent and incident frailty c2013 Dec a2091-90 v83 aBACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.
RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.
CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.
10aAge Factors10aAged10aAged, 80 and over10aAging10aBiomarkers10aCreatinine10aCross-Sectional Studies10aCystatin C10aFatigue10aFemale10aFrail Elderly10aGeriatric Assessment10aGlomerular Filtration Rate10aHumans10aIncidence10aIndependent Living10aKidney10aKidney Diseases10aLogistic Models10aMale10aMotor Activity10aMultivariate Analysis10aMuscle Weakness10aOdds Ratio10aPhenotype10aPrevalence10aProspective Studies10aRisk Factors10aTime Factors10aUnited States10aWeight Loss1 aDalrymple, Lorien, S1 aKatz, Ronit1 aRifkin, Dena, E1 aSiscovick, David1 aNewman, Anne, B1 aFried, Linda, F1 aSarnak, Mark, J1 aOdden, Michelle, C1 aShlipak, Michael, G uhttps://chs-nhlbi.org/node/613605590nas a2201609 4500008004100000022001400041245011100055210006900166260000900235300001300244490000600257520112100263653001201384653001901396653001701415653001201432653004001444653003101484653003401515653001601549653001101565653001101576653000901587653003601596100002601632700001801658700001601676700001701692700002001709700002601729700001901755700002301774700002201797700002101819700002101840700001901861700001801880700002401898700001201922700002001934700001801954700002001972700002201992700001702014700002002031700002502051700001902076700002102095700001802116700002502134700002202159700002002181700002202201700002402223700002202247700001902269700002202288700001902310700002002329700002102349700002102370700002402391700002202415700002402437700002002461700001902481700002402500700002202524700002002546700002202566700001802588700001802606700001702624700002102641700001902662700002002681700002202701700002502723700002002748700002502768700002102793700002202814700002402836700002302860700002202883700002302905700001702928700001902945700002202964700002302986700002803009700001503037700002103052700001903073700002003092700002203112700002103134700001903155700002803174700002603202700001703228700002003245700001903265700002303284700001803307700002103325700001803346700002303364700002403387700002103411700002003432700001903452700002203471700002003493700001503513700002003528700002103548700001603569700002103585700001903606700001803625700001903643700002003662700001703682700002203699700002203721700003003743700002003773700002003793700002503813700001903838700002103857700002103878710002403899710002103923856003603944 2013 eng d a1553-740400aMeta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.0 aMetaanalysis of genomewide association studies identifies six ne c2013 ae10037960 v93 aCalcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
10aAnimals10aBone and Bones10aBone Density10aCalcium10aEuropean Continental Ancestry Group10aGene Expression Regulation10aGenome-Wide Association Study10aHomeostasis10aHumans10aKidney10aMice10aPolymorphism, Single Nucleotide1 aO'Seaghdha, Conall, M1 aWu, Hongsheng1 aYang, Qiong1 aKapur, Karen1 aGuessous, Idris1 aZuber, Annie, Mercier1 aKöttgen, Anna1 aStoudmann, Candice1 aTeumer, Alexander1 aKutalik, Zoltán1 aMangino, Massimo1 aDehghan, Abbas1 aZhang, Weihua1 aEiriksdottir, Gudny1 aLi, Guo1 aTanaka, Toshiko1 aPortas, Laura1 aLopez, Lorna, M1 aHayward, Caroline1 aLohman, Kurt1 aMatsuda, Koichi1 aPadmanabhan, Sandosh1 aFirsov, Dmitri1 aSorice, Rossella1 aUlivi, Sheila1 aBrockhaus, Catharina1 aKleber, Marcus, E1 aMahajan, Anubha1 aErnst, Florian, D1 aGudnason, Vilmundur1 aLauner, Lenore, J1 aMace, Aurelien1 aBoerwinckle, Eric1 aArking, Dan, E1 aTanikawa, Chizu1 aNakamura, Yusuke1 aBrown, Morris, J1 aGaspoz, Jean-Michel1 aTheler, Jean-Marc1 aSiscovick, David, S1 aPsaty, Bruce, M1 aBergmann, Sven1 aVollenweider, Peter1 aVitart, Veronique1 aWright, Alan, F1 aZemunik, Tatijana1 aBoban, Mladen1 aKolcic, Ivana1 aNavarro, Pau1 aBrown, Edward, M1 aEstrada, Karol1 aDing, Jingzhong1 aHarris, Tamara, B1 aBandinelli, Stefania1 aHernandez, Dena1 aSingleton, Andrew, B1 aGirotto, Giorgia1 aRuggiero, Daniela1 ad'Adamo, Adamo, Pio1 aRobino, Antonietta1 aMeitinger, Thomas1 aMeisinger, Christa1 aDavies, Gail1 aStarr, John, M1 aChambers, John, C1 aBoehm, Bernhard, O1 aWinkelmann, Bernhard, R1 aHuang, Jie1 aMurgia, Federico1 aWild, Sarah, H1 aCampbell, Harry1 aMorris, Andrew, P1 aFranco, Oscar, H1 aHofman, Albert1 aUitterlinden, André, G1 aRivadeneira, Fernando1 aVölker, Uwe1 aHannemann, Anke1 aBiffar, Reiner1 aHoffmann, Wolfgang1 aShin, So-Youn1 aLescuyer, Pierre1 aHenry, Hughes1 aSchurmann, Claudia1 aMunroe, Patricia, B1 aGasparini, Paolo1 aPirastu, Nicola1 aCiullo, Marina1 aGieger, Christian1 aMärz, Winfried1 aLind, Lars1 aSpector, Tim, D1 aSmith, Albert, V1 aRudan, Igor1 aWilson, James, F1 aPolasek, Ozren1 aDeary, Ian, J1 aPirastu, Mario1 aFerrucci, Luigi1 aLiu, Yongmei1 aKestenbaum, Bryan1 aKooner, Jaspal, S1 aWitteman, Jacqueline, C M1 aNauck, Matthias1 aKao, Linda, W H1 aWallaschofski, Henri1 aBonny, Olivier1 aFox, Caroline, S1 aBochud, Murielle1 aSUNLIGHT Consortium1 aGEFOS Consortium uhttps://chs-nhlbi.org/node/629102403nas a2200361 4500008004100000022001400041245009100055210006900146260001700215300001000232490000700242520142400249653000901673653001001682653000901692653002101701653002101722653001101743653003101754653001101785653001101796653001101807653000901818653002401827653003101851100002601882700001601908700002101924700002001945700002101965700001901986856003602005 2014 eng d a1873-124400aDietary protein intake and change in estimated GFR in the Cardiovascular Health Study.0 aDietary protein intake and change in estimated GFR in the Cardio c2014 Jul-Aug a794-90 v303 aOBJECTIVE: With aging, kidney function declines, as evidenced by reduced glomerular filtration rate. It is controversial whether or not high protein intake accelerates this decline. The aim of this study was to determine whether high protein intake was associated with declines in kidney function among older patients.
METHODS: We examined whether dietary protein is associated with change in kidney function (mean follow-up 6.4 y [SD = 1.4, range = 2.5-7.9] in the Cardiovascular Health Study (N = 3623). We estimated protein intake using a food frequency questionnaire and estimated glomerular filtration rate from cystatin C. Associations between protein intake and kidney function were determined by linear and logistic regression models.
RESULTS: Average protein intake was 19% of energy intake (SD = 5%). Twenty-seven percent (n = 963) of study participants had rapid decline in kidney function, as defined by (ΔeGFRcysC > 3 mL•min•1.73 m(2)). Protein intake (characterized as g/d and % energy/d), was not associated with change in estimated glomerular filtration rate (P > 0.05 for all comparisons). There were also no significant associations when protein intake was separated by source (animal and vegetable).
CONCLUSION: These data suggest that higher protein intake does not have a major effect on kidney function decline among elderly men and women.
10aAged10aAging10aDiet10aDietary Proteins10aFeeding Behavior10aFemale10aGlomerular Filtration Rate10aHealth10aHumans10aKidney10aMale10aRegression Analysis10aSurveys and Questionnaires1 aBeasley, Jeannette, M1 aKatz, Ronit1 aShlipak, Michael1 aRifkin, Dena, E1 aSiscovick, David1 aKaplan, Robert uhttps://chs-nhlbi.org/node/654603491nas a2200493 4500008004100000022001400041245012600055210006900181260001300250300001100263490000600274520211000280653002402390653001602414653000902430653002202439653001602461653001502477653001502492653001502507653001102522653003002533653003102563653002002594653001102614653002302625653001102648653002502659653000902684653001402693653003202707653002402739653001702763653001702780100002302797700001602820700001902836700002002855700002402875700002102899700002102920700002002941856003602961 2014 eng d a1555-905X00aFibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals.0 aFibroblast growth factor23 and the longterm risk of hospitalasso c2014 Feb a239-460 v93 aBACKGROUND AND OBJECTIVES: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.
RESULTS: The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).
CONCLUSIONS: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.
10aAcute Kidney Injury10aAge Factors10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCreatinine10aCystatin C10aFemale10aFibroblast Growth Factors10aGlomerular Filtration Rate10aHospitalization10aHumans10aIndependent Living10aKidney10aLongitudinal Studies10aMale10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Factors10aTime Factors1 aBrown, Jeremiah, R1 aKatz, Ronit1 aIx, Joachim, H1 ade Boer, Ian, H1 aSiscovick, David, S1 aGrams, Morgan, E1 aShlipak, Michael1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/630802589nas a2200361 4500008004100000022001400041245009100055210006900146260001600215300001000231490000800241520158100249653000901830653002801839653001401867653002401881653001501905653001101920653003101931653001801962653001101980653001101991653002002002653000902022653002902031100002002060700002402080700002002104700001602124700002802140700002302168856003602191 2014 eng d a1476-625600aKidney function and cognitive health in older adults: the Cardiovascular Health Study.0 aKidney function and cognitive health in older adults the Cardiov c2014 Jul 01 a68-750 v1803 aRecent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.
10aAged10aCardiovascular Diseases10aCognition10aCognition Disorders10aCystatin C10aFemale10aGlomerular Filtration Rate10aHealth Status10aHumans10aKidney10aKidney Diseases10aMale10aNeuropsychological Tests1 aDarsie, Brendan1 aShlipak, Michael, G1 aSarnak, Mark, J1 aKatz, Ronit1 aFitzpatrick, Annette, L1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/636403245nas a2200517 4500008004100000022001400041245011100055210006900166260001300235300001100248490000800259520180600267653000902073653002202082653001902104653002302123653002802146653002102174653002102195653002702216653002202243653001102265653001102276653001702287653001102304653002002315653001102335653000902346653003102355653001202386653002202398653001702420100002302437700002402460700002402484700001602508700002502524700002102549700001902570700002002589700002402609700001802633700002002651700002002671856003602691 2014 eng d a1879-148400aRisk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study.0 aRisk factors for cardiovascular disease across the spectrum of o c2014 Nov a336-420 v2373 aOBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.
METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).
RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).
CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
10aAged10aAged, 80 and over10aBlood Pressure10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCholesterol, LDL10aDiabetes Complications10aDiabetes Mellitus10aFemale10aHumans10aInflammation10aKidney10aKidney Diseases10aLipids10aMale10aNatriuretic Peptide, Brain10aObesity10aPeptide Fragments10aRisk Factors1 aOdden, Michelle, C1 aShlipak, Michael, G1 aWhitson, Heather, E1 aKatz, Ronit1 aKearney, Patricia, M1 adeFilippi, Chris1 aShastri, Shani1 aSarnak, Mark, J1 aSiscovick, David, S1 aCushman, Mary1 aPsaty, Bruce, M1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/658802886nas a2200445 4500008004100000022001400041245008300055210006900138260001300207300001100220490000700231520166800238653001601906653000901922653002201931653001001953653004301963653001902006653001102025653000902036653002502045653001202070653002902082653001102111653001102122653000902133653000902142653003202151653001702183100002102200700002202221700002102243700002402264700002202288700002502310700002102335700002802356700002002384856003602404 2015 eng d a1758-535X00aMultisystem physiologic impairments and changes in gait speed of older adults.0 aMultisystem physiologic impairments and changes in gait speed of c2015 Mar a319-240 v703 aBACKGROUND: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals.
METHODS: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models.
RESULTS: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, -0.006).
CONCLUSIONS: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.
10aAge Factors10aAged10aAged, 80 and over10aBrain10aCardiovascular Physiological Phenomena10aCohort Studies10aFemale10aGait10aGeriatric Assessment10aGlucose10aHealth Status Indicators10aHumans10aKidney10aLung10aMale10aSensitivity and Specificity10aTime Factors1 aRosso, Andrea, L1 aSanders, Jason, L1 aArnold, Alice, M1 aBoudreau, Robert, M1 aHirsch, Calvin, H1 aCarlson, Michelle, C1 aRosano, Caterina1 aKritchevsky, Stephen, B1 aNewman, Anne, B uhttps://chs-nhlbi.org/node/659603861nas a2200565 4500008004100000022001400041245010700055210006900162260001500231300001100246490000700257520230700264653001602571653000902587653001002596653001502606653001502621653002402636653001102660653003102671653001102702653001402713653001102727653001802738653002502756653000902781653003102790653002202821653003002843653001402873653003202887653002402919653003302943653001702976653001702993653001503010653001803025653001803043100001803061700001603079700002203095700001703117700002703134700002203161700001703183700001703200700002103217700002103238856003603259 2015 eng d a1555-905X00aNT-proBNP and troponin T and risk of rapid kidney function decline and incident CKD in elderly adults.0 aNTproBNP and troponin T and risk of rapid kidney function declin c2015 Feb 6 a205-140 v103 aBACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.
RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).
CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.
10aAge Factors10aAged10aAging10aBiomarkers10aCystatin C10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aKidney10aLinear Models10aLongitudinal Studies10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aPredictive Value of Tests10aPrognosis10aProportional Hazards Models10aProspective Studies10aRenal Insufficiency, Chronic10aRisk Factors10aTime Factors10aTroponin T10aUnited States10aUp-Regulation1 aBansal, Nisha1 aKatz, Ronit1 aDalrymple, Lorien1 ade Boer, Ian1 aDeFilippi, Christopher1 aKestenbaum, Bryan1 aPark, Meyeon1 aSarnak, Mark1 aSeliger, Stephen1 aShlipak, Michael uhttps://chs-nhlbi.org/node/666102980nas a2200433 4500008004100000022001400041245009400055210006900149260001600218300001400234490000800248520176800256653001402024653000902038653002202047653002802069653001102097653003002108653003102138653001102169653001102180653000902191653001602200653001302216653003302229653001702262100001802279700002002297700002102317700002202338700002002360700003002380700002002410700001902430700002202449700002102471700001802492856003602510 2017 eng d a1945-719700aFibroblast Growth Factor 23, Mineral Metabolism, and Adiposity in Normal Kidney Function.0 aFibroblast Growth Factor 23 Mineral Metabolism and Adiposity in c2017 Apr 01 a1387-13950 v1023 aContext: Obesity is associated with poor bone mineralization and quality. Fibroblast growth factor 23 (FGF23) plays an important role in skeletal physiology.
Objective: To test hypothesis that greater adiposity results in higher FGF23 levels among individuals with normal estimated glomerular filtration rate (eGFR).
Design, Setting, Participants: Cross-sectional analyses among participants with eGFR ≥60 mL/min/1.73m2. We assessed the association between crude [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR); n = 5610] and refined (abdominal adipose tissue area by computed tomography; n = 1313) measures of adiposity and FGF23 using multivariable linear regression.
Main Outcome Measure: Serum FGF23.
Results: FGF23 was higher across BMI categories (BMI <25: 37.7; BMI 25 to 29.99: 38.7; BMI 30 to 39.99: 39.8; BMI ≥40: 40.9 pg/mL, unadjusted P trend < 0.0001). The association between BMI and FGF23 was independent of known confounders of FGF23 (adjusted β = +7.2% higher FGF23 per 10 kg/m2; P < 0.0001). Similar results were observed using WC and WHR. Abdominal adipose tissue area was also independently associated with higher FGF23 (P < 0.01). Notably, the positive associations between FGF23 and adiposity were observed despite the fact that eGFR did not decline and serum phosphate levels did not increase with adiposity.
Conclusion: In a large cohort with normal kidney function, adiposity was associated with higher FGF23 levels independent of known confounders, including eGFR and phosphate. Further studies are needed to evaluate the causes of higher FGF23 in settings of greater adiposity and the potential impact on skeletal health.
10aAdiposity10aAged10aAged, 80 and over10aCross-Sectional Studies10aFemale10aFibroblast Growth Factors10aGlomerular Filtration Rate10aHumans10aKidney10aMale10aMiddle Aged10aMinerals10aRenal Insufficiency, Chronic10aRisk Factors1 aZaheer, Sarah1 ade Boer, Ian, H1 aAllison, Matthew1 aBrown, Jenifer, M1 aPsaty, Bruce, M1 aRobinson-Cohen, Cassianne1 aMichos, Erin, D1 aIx, Joachim, H1 aKestenbaum, Bryan1 aSiscovick, David1 aVaidya, Anand uhttps://chs-nhlbi.org/node/760105906nas a2201705 4500008004100000022001400041245008700055210006900142260001500211300000900226490000700235520117400242653001001416653000901426653001601435653002001451653001101471653003101482653001101513653003401524653001101558653002601569653002401595653000901619653002201628653001601650653003301666653002601699100002201725700001801747700002901765700002101794700001901815700001601834700001901850700001201869700002101881700003301902700001901935700002601954700002201980700001902002700001902021700002302040700002102063700002102084700002702105700002202132700001802154700002202172700002102194700001802215700001802233700001902251700001802270700001902288700002502307700002602332700002102358700001902379700002202398700002202420700002002442700002002462700001702482700002102499700001202520700001502532700002102547700001902568700002202587700002202609700002002631700002102651700001902672700002002691700002202711700001902733700001602752700002002768700002002788700002702808700002402835700001802859700002202877700002102899700002202920700001802942700002402960700002102984700002203005700001503027700001303042700001703055700002703072700001703099700002203116700001503138700002503153700002003178700002503198700002403223700001703247700002503264700002003289700002103309700002103330700002003351700002103371700002003392700002303412700002203435700002003457700002103477700002003498700001903518700002003537700002303557700002203580700002303602700002303625700002203648700002403670700002403694700002603718700003503744700001903779700001803798700002103816700002403837700002403861700003003885700001403915700001703929700001503946700002003961700001703981700002603998700002104024700001904045700002204064710003504086710004304121856003604164 2021 eng d a2041-172300aMeta-analyses identify DNA methylation associated with kidney function and damage.0 aMetaanalyses identify DNA methylation associated with kidney fun c2021 12 09 a71740 v123 aChronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
10aAdult10aAged10aCpG Islands10aDNA Methylation10aFemale10aGlomerular Filtration Rate10aHumans10aInterferon Regulatory Factors10aKidney10aKidney Function Tests10aLIM Domain Proteins10aMale10aMembrane Proteins10aMiddle Aged10aRenal Insufficiency, Chronic10aTranscription Factors1 aSchlosser, Pascal1 aTin, Adrienne1 aMatias-Garcia, Pamela, R1 aThio, Chris, H L1 aJoehanes, Roby1 aLiu, Hongbo1 aWeihs, Antoine1 aYu, Zhi1 aHoppmann, Anselm1 aGrundner-Culemann, Franziska1 aMin, Josine, L1 aAdeyemo, Adebowale, A1 aAgyemang, Charles1 aArnlöv, Johan1 aAziz, Nasir, A1 aBaccarelli, Andrea1 aBochud, Murielle1 aBrenner, Hermann1 aBreteler, Monique, M B1 aCarmeli, Cristian1 aChaker, Layal1 aChambers, John, C1 aCole, Shelley, A1 aCoresh, Josef1 aCorre, Tanguy1 aCorrea, Adolfo1 aCox, Simon, R1 ade Klein, Niek1 aDelgado, Graciela, E1 aDomingo-Relloso, Arce1 aEckardt, Kai-Uwe1 aEkici, Arif, B1 aEndlich, Karlhans1 aEvans, Kathryn, L1 aFloyd, James, S1 aFornage, Myriam1 aFranke, Lude1 aFraszczyk, Eliza1 aGao, Xu1 aGào, Xīn1 aGhanbari, Mohsen1 aGhasemi, Sahar1 aGieger, Christian1 aGreenland, Philip1 aGrove, Megan, L1 aHarris, Sarah, E1 aHemani, Gibran1 aHenneman, Peter1 aHerder, Christian1 aHorvath, Steve1 aHou, Lifang1 aHurme, Mikko, A1 aHwang, Shih-Jen1 aJarvelin, Marjo-Riitta1 aKardia, Sharon, L R1 aKasela, Silva1 aKleber, Marcus, E1 aKoenig, Wolfgang1 aKooner, Jaspal, S1 aKramer, Holly1 aKronenberg, Florian1 aKuhnel, Brigitte1 aLehtimäki, Terho1 aLind, Lars1 aLiu, Dan1 aLiu, Yongmei1 aLloyd-Jones, Donald, M1 aLohman, Kurt1 aLorkowski, Stefan1 aLu, Ake, T1 aMarioni, Riccardo, E1 aMärz, Winfried1 aMcCartney, Daniel, L1 aMeeks, Karlijn, A C1 aMilani, Lili1 aMishra, Pashupati, P1 aNauck, Matthias1 aNavas-Acien, Ana1 aNowak, Christoph1 aPeters, Annette1 aProkisch, Holger1 aPsaty, Bruce, M1 aRaitakari, Olli, T1 aRatliff, Scott, M1 aReiner, Alex, P1 aRosas, Sylvia, E1 aSchöttker, Ben1 aSchwartz, Joel1 aSedaghat, Sanaz1 aSmith, Jennifer, A1 aSotoodehnia, Nona1 aStocker, Hannah, R1 aStringhini, Silvia1 aSundström, Johan1 aSwenson, Brenton, R1 aTellez-Plaza, Maria1 avan Meurs, Joyce, B J1 avan Vliet-Ostaptchouk, Jana, V1 aVenema, Andrea1 aVerweij, Niek1 aWalker, Rosie, M1 aWielscher, Matthias1 aWinkelmann, Juliane1 aWolffenbuttel, Bruce, H R1 aZhao, Wei1 aZheng, Yinan1 aLoh, Marie1 aSnieder, Harold1 aLevy, Daniel1 aWaldenberger, Melanie1 aSusztak, Katalin1 aKöttgen, Anna1 aTeumer, Alexander1 aEstonian Biobank Research Team1 aGenetics of DNA Methylation Consortium uhttps://chs-nhlbi.org/node/900212282nas a2204021 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2022 eng d a2399-364200aDifferential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.0 aDifferential and shared genetic effects on kidney function betwe c2022 Jun 13 a5800 v53 aReduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (n = 178,691, n = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
10aCreatinine10aDiabetes Mellitus10aDiabetic Nephropathies10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKidney1 aWinkler, Thomas, W1 aRasheed, Humaira1 aTeumer, Alexander1 aGorski, Mathias1 aRowan, Bryce, X1 aStanzick, Kira, J1 aThomas, Laurent, F1 aTin, Adrienne1 aHoppmann, Anselm1 aChu, Audrey, Y1 aTayo, Bamidele1 aThio, Chris, H L1 aCusi, Daniele1 aChai, Jin-Fang1 aSieber, Karsten, B1 aHorn, Katrin1 aLi, Man1 aScholz, Markus1 aCocca, Massimiliano1 aWuttke, Matthias1 avan der Most, Peter, J1 aYang, Qiong1 aGhasemi, Sahar1 aNutile, Teresa1 aLi, Yong1 aPontali, Giulia1 aGünther, Felix1 aDehghan, Abbas1 aCorrea, Adolfo1 aParsa, Afshin1 aFeresin, Agnese1 ade Vries, Aiko, P J1 aZonderman, Alan, B1 aSmith, Albert, V1 aOldehinkel, Albertine, J1 aDe Grandi, Alessandro1 aRosenkranz, Alexander, R1 aFranke, Andre1 aTeren, Andrej1 aMetspalu, Andres1 aHicks, Andrew, A1 aMorris, Andrew, P1 aTönjes, Anke1 aMorgan, Anna1 aPodgornaia, Anna, I1 aPeters, Annette1 aKörner, Antje1 aMahajan, Anubha1 aCampbell, Archie1 aFreedman, Barry, I1 aSpedicati, Beatrice1 aPonte, Belen1 aSchöttker, Ben1 aBrumpton, Ben1 aBanas, Bernhard1 aKrämer, Bernhard, K1 aJung, Bettina1 aÅsvold, Bjørn, Olav1 aSmith, Blair, H1 aNing, Boting1 aPenninx, Brenda, W J H1 aVanderwerff, Brett, R1 aPsaty, Bruce, M1 aKammerer, Candace, M1 aLangefeld, Carl, D1 aHayward, Caroline1 aSpracklen, Cassandra, N1 aRobinson-Cohen, Cassianne1 aHartman, Catharina, A1 aLindgren, Cecilia, M1 aWang, Chaolong1 aSabanayagam, Charumathi1 aHeng, Chew-Kiat1 aLanzani, Chiara1 aKhor, Chiea-Chuen1 aCheng, Ching-Yu1 aFuchsberger, Christian1 aGieger, Christian1 aShaffer, Christian, M1 aSchulz, Christina-Alexandra1 aWiller, Cristen, J1 aChasman, Daniel, I1 aGudbjartsson, Daniel, F1 aRuggiero, Daniela1 aToniolo, Daniela1 aCzamara, Darina1 aPorteous, David, J1 aWaterworth, Dawn, M1 aMascalzoni, Deborah1 aMook-Kanamori, Dennis, O1 aReilly, Dermot, F1 aDaw, Warwick1 aHofer, Edith1 aBoerwinkle, Eric1 aSalvi, Erika1 aBottinger, Erwin, P1 aTai, E-Shyong1 aCatamo, Eulalia1 aRizzi, Federica1 aGuo, Feng1 aRivadeneira, Fernando1 aGuilianini, Franco1 aSveinbjornsson, Gardar1 aEhret, Georg1 aWaeber, Gérard1 aBiino, Ginevra1 aGirotto, Giorgia1 aPistis, Giorgio1 aNadkarni, Girish, N1 aDelgado, Graciela, E1 aMontgomery, Grant, W1 aSnieder, Harold1 aCampbell, Harry1 aWhite, Harvey, D1 aGao, He1 aStringham, Heather, M1 aSchmidt, Helena1 aLi, Hengtong1 aBrenner, Hermann1 aHolm, Hilma1 aKirsten, Holgen1 aKramer, Holly1 aRudan, Igor1 aNolte, Ilja, M1 aTzoulaki, Ioanna1 aOlafsson, Isleifur1 aMartins, Jade1 aCook, James, P1 aWilson, James, F1 aHalbritter, Jan1 aFelix, Janine, F1 aDivers, Jasmin1 aKooner, Jaspal, S1 aLee, Jeannette, Jen-Mai1 aO'Connell, Jeffrey1 aRotter, Jerome, I1 aLiu, Jianjun1 aXu, Jie1 aThiery, Joachim1 aArnlöv, Johan1 aKuusisto, Johanna1 aJakobsdottir, Johanna1 aTremblay, Johanne1 aChambers, John, C1 aWhitfield, John, B1 aGaziano, John, M1 aMarten, Jonathan1 aCoresh, Josef1 aJonas, Jost, B1 aMychaleckyj, Josyf, C1 aChristensen, Kaare1 aEckardt, Kai-Uwe1 aMohlke, Karen, L1 aEndlich, Karlhans1 aDittrich, Katalin1 aRyan, Kathleen, A1 aRice, Kenneth, M1 aTaylor, Kent, D1 aHo, Kevin1 aNikus, Kjell1 aMatsuda, Koichi1 aStrauch, Konstantin1 aMiliku, Kozeta1 aHveem, Kristian1 aLind, Lars1 aWallentin, Lars1 aYerges-Armstrong, Laura, M1 aRaffield, Laura, M1 aPhillips, Lawrence, S1 aLauner, Lenore, J1 aLyytikäinen, Leo-Pekka1 aLange, Leslie, A1 aCitterio, Lorena1 aKlaric, Lucija1 aIkram, Arfan, M1 aIsing, Marcus1 aKleber, Marcus, E1 aFrancescatto, Margherita1 aConcas, Maria, Pina1 aCiullo, Marina1 aPiratsu, Mario1 aOrho-Melander, Marju1 aLaakso, Markku1 aLoeffler, Markus1 aPerola, Markus1 ade Borst, Martin, H1 aGögele, Martin1 aLa Bianca, Martina1 aLukas, Mary, Ann1 aFeitosa, Mary, F1 aBiggs, Mary, L1 aWojczynski, Mary, K1 aKavousi, Maryam1 aKanai, Masahiro1 aAkiyama, Masato1 aYasuda, Masayuki1 aNauck, Matthias1 aWaldenberger, Melanie1 aChee, Miao-Li1 aChee, Miao-Ling1 aBoehnke, Michael1 aPreuss, Michael, H1 aStumvoll, Michael1 aProvince, Michael, A1 aEvans, Michele, K1 aO'Donoghue, Michelle, L1 aKubo, Michiaki1 aKähönen, Mika1 aKastarinen, Mika1 aNalls, Mike, A1 aKuokkanen, Mikko1 aGhanbari, Mohsen1 aBochud, Murielle1 aJosyula, Navya, Shilpa1 aMartin, Nicholas, G1 aTan, Nicholas, Y Q1 aPalmer, Nicholette, D1 aPirastu, Nicola1 aSchupf, Nicole1 aVerweij, Niek1 aHutri-Kähönen, Nina1 aMononen, Nina1 aBansal, Nisha1 aDevuyst, Olivier1 aMelander, Olle1 aRaitakari, Olli, T1 aPolasek, Ozren1 aManunta, Paolo1 aGasparini, Paolo1 aMishra, Pashupati, P1 aSulem, Patrick1 aMagnusson, Patrik, K E1 aElliott, Paul1 aRidker, Paul, M1 aHamet, Pavel1 aSvensson, Per, O1 aJoshi, Peter, K1 aKovacs, Peter1 aPramstaller, Peter, P1 aRossing, Peter1 aVollenweider, Peter1 aHarst, Pim1 aDorajoo, Rajkumar1 aSim, Ralene, Z H1 aBurkhardt, Ralph1 aTao, Ran1 aNoordam, Raymond1 aMägi, Reedik1 aSchmidt, Reinhold1 ade Mutsert, Renée1 aRueedi, Rico1 avan Dam, Rob, M1 aCarroll, Robert, J1 aGansevoort, Ron, T1 aLoos, Ruth, J F1 aFelicita, Sala, Cinzia1 aSedaghat, Sanaz1 aPadmanabhan, Sandosh1 aFreitag-Wolf, Sandra1 aPendergrass, Sarah, A1 aGraham, Sarah, E1 aGordon, Scott, D1 aHwang, Shih-Jen1 aKerr, Shona, M1 aVaccargiu, Simona1 aPatil, Snehal, B1 aHallan, Stein1 aBakker, Stephan, J L1 aLim, Su-Chi1 aLucae, Susanne1 aVogelezang, Suzanne1 aBergmann, Sven1 aCorre, Tanguy1 aAhluwalia, Tarunveer, S1 aLehtimäki, Terho1 aBoutin, Thibaud, S1 aMeitinger, Thomas1 aWong, Tien-Yin1 aBergler, Tobias1 aRabelink, Ton, J1 aEsko, Tõnu1 aHaller, Toomas1 aThorsteinsdottir, Unnur1 aVölker, Uwe1 aFoo, Valencia, Hui Xian1 aSalomaa, Veikko1 aVitart, Veronique1 aGiedraitis, Vilmantas1 aGudnason, Vilmundur1 aJaddoe, Vincent, W V1 aHuang, Wei1 aZhang, Weihua1 aBin Wei, Wen1 aKiess, Wieland1 aMärz, Winfried1 aKoenig, Wolfgang1 aLieb, Wolfgang1 aGào, Xīn1 aSim, Xueling1 aWang, Ya, Xing1 aFriedlander, Yechiel1 aTham, Yih-Chung1 aKamatani, Yoichiro1 aOkada, Yukinori1 aMilaneschi, Yuri1 aYu, Zhi1 aStark, Klaus, J1 aStefansson, Kari1 aBöger, Carsten, A1 aHung, Adriana, M1 aKronenberg, Florian1 aKöttgen, Anna1 aPattaro, Cristian1 aHeid, Iris, M1 aLifeLines Cohort Study1 aDiscovEHR/MyCode study1 aVA Million Veteran Program uhttps://chs-nhlbi.org/node/911207235nas a2202173 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2024 eng d a2041-172300aX-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.0 aXchromosome and kidney function evidence from a multitrait genet c2024 Jan 18 a5860 v153 aX-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
10aAndrogens10aChromosomes, Human, X10aFemale10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aHumans10aKidney10aMale10aPolymorphism, Single Nucleotide10aResponse Elements10aTetraspanins1 aScholz, Markus1 aHorn, Katrin1 aPott, Janne1 aWuttke, Matthias1 aKühnapfel, Andreas1 aNasr, Kamal1 aKirsten, Holger1 aLi, Yong1 aHoppmann, Anselm1 aGorski, Mathias1 aGhasemi, Sahar1 aLi, Man1 aTin, Adrienne1 aChai, Jin-Fang1 aCocca, Massimiliano1 aWang, Judy1 aNutile, Teresa1 aAkiyama, Masato1 aÅsvold, Bjørn, Olav1 aBansal, Nisha1 aBiggs, Mary, L1 aBoutin, Thibaud1 aBrenner, Hermann1 aBrumpton, Ben1 aBurkhardt, Ralph1 aCai, Jianwen1 aCampbell, Archie1 aCampbell, Harry1 aChalmers, John1 aChasman, Daniel, I1 aChee, Miao, Ling1 aChee, Miao, Li1 aChen, Xu1 aCheng, Ching-Yu1 aCifkova, Renata1 aDaviglus, Martha1 aDelgado, Graciela1 aDittrich, Katalin1 aEdwards, Todd, L1 aEndlich, Karlhans1 aGaziano, Michael1 aGiri, Ayush1 aGiulianini, Franco1 aGordon, Scott, D1 aGudbjartsson, Daniel, F1 aHallan, Stein1 aHamet, Pavel1 aHartman, Catharina, A1 aHayward, Caroline1 aHeid, Iris, M1 aHellwege, Jacklyn, N1 aHolleczek, Bernd1 aHolm, Hilma1 aHutri-Kähönen, Nina1 aHveem, Kristian1 aIsermann, Berend1 aJonas, Jost, B1 aJoshi, Peter, K1 aKamatani, Yoichiro1 aKanai, Masahiro1 aKastarinen, Mika1 aKhor, Chiea, Chuen1 aKiess, Wieland1 aKleber, Marcus, E1 aKörner, Antje1 aKovacs, Peter1 aKrajcoviechova, Alena1 aKramer, Holly1 aKrämer, Bernhard, K1 aKuokkanen, Mikko1 aKähönen, Mika1 aLange, Leslie, A1 aLash, James, P1 aLehtimäki, Terho1 aLi, Hengtong1 aLin, Bridget, M1 aLiu, Jianjun1 aLoeffler, Markus1 aLyytikäinen, Leo-Pekka1 aMagnusson, Patrik, K E1 aMartin, Nicholas, G1 aMatsuda, Koichi1 aMilaneschi, Yuri1 aMishra, Pashupati, P1 aMononen, Nina1 aMontgomery, Grant, W1 aMook-Kanamori, Dennis, O1 aMychaleckyj, Josyf, C1 aMärz, Winfried1 aNauck, Matthias1 aNikus, Kjell1 aNolte, Ilja, M1 aNoordam, Raymond1 aOkada, Yukinori1 aOlafsson, Isleifur1 aOldehinkel, Albertine, J1 aPenninx, Brenda, W J H1 aPerola, Markus1 aPirastu, Nicola1 aPolasek, Ozren1 aPorteous, David, J1 aPoulain, Tanja1 aPsaty, Bruce, M1 aRabelink, Ton, J1 aRaffield, Laura, M1 aRaitakari, Olli, T1 aRasheed, Humaira1 aReilly, Dermot, F1 aRice, Kenneth, M1 aRichmond, Anne1 aRidker, Paul, M1 aRotter, Jerome, I1 aRudan, Igor1 aSabanayagam, Charumathi1 aSalomaa, Veikko1 aSchneiderman, Neil1 aSchöttker, Ben1 aSims, Mario1 aSnieder, Harold1 aStark, Klaus, J1 aStefansson, Kari1 aStocker, Hannah1 aStumvoll, Michael1 aSulem, Patrick1 aSveinbjornsson, Gardar1 aSvensson, Per, O1 aTai, E-Shyong1 aTaylor, Kent, D1 aTayo, Bamidele, O1 aTeren, Andrej1 aTham, Yih-Chung1 aThiery, Joachim1 aThio, Chris, H L1 aThomas, Laurent, F1 aTremblay, Johanne1 aTönjes, Anke1 avan der Most, Peter, J1 aVitart, Veronique1 aVölker, Uwe1 aWang, Ya, Xing1 aWang, Chaolong1 aBin Wei, Wen1 aWhitfield, John, B1 aWild, Sarah, H1 aWilson, James, F1 aWinkler, Thomas, W1 aWong, Tien-Yin1 aWoodward, Mark1 aSim, Xueling1 aChu, Audrey, Y1 aFeitosa, Mary, F1 aThorsteinsdottir, Unnur1 aHung, Adriana, M1 aTeumer, Alexander1 aFranceschini, Nora1 aParsa, Afshin1 aKöttgen, Anna1 aSchlosser, Pascal1 aPattaro, Cristian uhttps://chs-nhlbi.org/node/9579