03491nas 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 a
BACKGROUND 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/630803482nas a2200541 4500008004100000022001400041245011500055210006900170260001300239300001200252490000700264520194200271653002402213653001502237653001002252653002202262653002102284653000902305653001602314653003402330653004002364653001102404653003102415653001102446653001402457653000902471653001602480653003002496653001402526653003002540653002102570653001602591100002102607700001902628700002402647700002302671700001702694700002202711700001902733700001802752700002002770700001802790700002002808700002502828700002202853710002902875856003602904 2015 eng d a1523-683800aA Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.0 aMetaanalysis of the Association of Estimated GFR Albuminuria Age c2015 Oct a591-6010 v663 aBACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).
STUDY DESIGN: Collaborative meta-analysis.
SETTING & POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).
SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events.
PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions.
OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.
RESULTS: 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.
LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.
CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.
10aAcute Kidney Injury10aAdolescent10aAdult10aAfrican Americans10aAge Distribution10aAged10aAlbuminuria10aContinental Population Groups10aEuropean Continental Ancestry Group10aFemale10aGlomerular Filtration Rate10aHumans10aIncidence10aMale10aMiddle Aged10aPredictive Value of Tests10aPrognosis10aSeverity of Illness Index10aSex Distribution10aYoung Adult1 aGrams, Morgan, E1 aSang, Yingying1 aBallew, Shoshana, H1 aGansevoort, Ron, T1 aKimm, Heejin1 aKovesdy, Csaba, P1 aNaimark, David1 aOien, Cecilia1 aSmith, David, H1 aCoresh, Josef1 aSarnak, Mark, J1 aStengel, Bénédicte1 aTonelli, Marcello1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/679703439nas a2200469 4500008004100000022001400041245013200055210006900187260001300256300001100269490000700280520210300287653002402390653001002414653000902424653001602433653002202449653002402471653001102495653003102506653001102537653001702548653001402565653002802579653000902607653001602616653001402632653003302646100002202679700002102701700001902722700001702741700002002758700002202778700001802800700002302818700002102841700002202862700002002884710002902904856003602933 2015 eng d a1523-683800aA Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.0 aMetaanalysis of the Association of Estimated GFR Albuminuria Dia c2015 Oct a602-120 v663 aBACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.
STUDY DESIGN: Meta-analysis of cohort studies.
SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.
SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.
PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.
OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.
RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.
LIMITATIONS: AKI identified by diagnostic code.
CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
10aAcute Kidney Injury10aAdult10aAged10aComorbidity10aDiabetes Mellitus10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHumans10aHypertension10aIncidence10aKidney Failure, Chronic10aMale10aMiddle Aged10aPrognosis10aRenal Insufficiency, Chronic1 aJames, Matthew, T1 aGrams, Morgan, E1 aWoodward, Mark1 aElley, Raina1 aGreen, Jamie, A1 aWheeler, David, C1 ade Jong, Paul1 aGansevoort, Ron, T1 aLevey, Andrew, S1 aWarnock, David, G1 aSarnak, Mark, J1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/679603720nas a2200445 4500008004100000022001400041245015900055210006900214260001600283520232600299100002102625700002102646700002102667700001802688700002102706700002102727700002302748700002602771700002102797700002102818700002402839700001702863700002402880700002302904700002102927700002402948700002302972700002702995700002103022700002003043700002403063700001703087700002503104700002103129700002203150700001903172700001803191710002903209856003603238 2018 eng d a1523-683800aRelationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium.0 aRelationship of Estimated GFR and Albuminuria to Concurrent Labo c2018 Oct 193 aRATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.
STUDY DESIGN: Cross-sectional individual participant-level analyses in a global consortium.
SETTING & STUDY POPULATIONS: 17 CKD and 38 general population and high-risk cohorts.
SELECTION CRITERIA FOR STUDIES: Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.
DATA EXTRACTION: Data were obtained and analyzed between July 2015 and January 2018.
ANALYTICAL APPROACH: We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.
RESULTS: The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).
LIMITATIONS: Variations in study era, health care delivery system, typical diet, and laboratory assays.
CONCLUSIONS: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.
1 aInker, Lesley, A1 aGrams, Morgan, E1 aLevey, Andrew, S1 aCoresh, Josef1 aCirillo, Massimo1 aCollins, John, F1 aGansevoort, Ron, T1 aGutierrez, Orlando, M1 aHamano, Takayuki1 aHeine, Gunnar, H1 aIshikawa, Shizukiyo1 aJee, Sun, Ha1 aKronenberg, Florian1 aLandray, Martin, J1 aMiura, Katsuyuki1 aNadkarni, Girish, N1 aPeralta, Carmen, A1 aRothenbacher, Dietrich1 aSchaeffner, Elke1 aSedaghat, Sanaz1 aShlipak, Michael, G1 aZhang, Luxia1 avan Zuilen, Arjan, D1 aHallan, Stein, I1 aKovesdy, Csaba, P1 aWoodward, Mark1 aLevin, Adeera1 aCKD Prognosis Consortium uhttps://chs-nhlbi.org/node/791503207nas a2200337 4500008004100000022001400041245013200055210006900187260001600256300001200272490000800284520218000292100002602472700002202498700002102520700002502541700002102566700001702587700002402604700001702628700002102645700002002666700002402686700002402710700002102734700002202755700002102777700001702798700001802815856003602833 2019 eng d a1535-497000aAlbuminuria, Lung Function Decline, and Risk of Incident Chronic Obstructive Pulmonary Disease. The NHLBI Pooled Cohorts Study.0 aAlbuminuria Lung Function Decline and Risk of Incident Chronic O c2019 Feb 01 a321-3320 v1993 aRATIONALE: Chronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.
OBJECTIVES: To test whether albuminuria was associated with lung function decline and incident CLRDs.
METHODS: Six U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.
MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.
CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.
1 aOelsner, Elizabeth, C1 aBalte, Pallavi, P1 aGrams, Morgan, E1 aCassano, Patricia, A1 aJacobs, David, R1 aBarr, Graham1 aBurkart, Kristin, M1 aKalhan, Ravi1 aKronmal, Richard1 aLoehr, Laura, R1 aO'Connor, George, T1 aSchwartz, Joseph, E1 aShlipak, Michael1 aTracy, Russell, P1 aTsai, Michael, Y1 aWhite, Wendy1 aYende, Sachin uhttps://chs-nhlbi.org/node/7980