@article {7380, title = {Age and association of kidney measures with mortality and end-stage renal disease.}, journal = {JAMA}, volume = {308}, year = {2012}, month = {2012 Dec 12}, pages = {2349-60}, abstract = {

CONTEXT: 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.

}, keywords = {Adolescent, Adult, Age Factors, Aged, Albuminuria, Cohort Studies, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Male, Middle Aged, Risk, Young Adult}, issn = {1538-3598}, doi = {10.1001/jama.2012.16817}, author = {Hallan, Stein I and Matsushita, Kunihiro and Sang, Yingying and Mahmoodi, Bakhtawar K and Black, Corri and Ishani, Areef and Kleefstra, Nanne and Naimark, David and Roderick, Paul and Tonelli, Marcello and Wetzels, Jack F M and Astor, Brad C and Gansevoort, Ron T and Levin, Adeera and Wen, Chi-Pang and Coresh, Josef} } @article {6086, title = {Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.}, journal = {Lancet}, volume = {380}, year = {2012}, month = {2012 Nov 10}, pages = {1662-73}, abstract = {

BACKGROUND: Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown.

METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes.

FINDINGS: We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8{\textperiodcentered}5 years (SD 5{\textperiodcentered}0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9{\textperiodcentered}2 years (SD 4{\textperiodcentered}9). In the general and high-risk cohorts, mortality risks were 1{\textperiodcentered}2-1{\textperiodcentered}9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1{\textperiodcentered}73 m(2) [vs 95 mL/min per 1{\textperiodcentered}73 m(2)], HR 1{\textperiodcentered}35; 95\% CI 1{\textperiodcentered}18-1{\textperiodcentered}55; vs 1{\textperiodcentered}33; 1{\textperiodcentered}19-1{\textperiodcentered}48 and at ACR 30 mg/g [vs 5 mg/g], 1{\textperiodcentered}50; 1{\textperiodcentered}35-1{\textperiodcentered}65 vs 1{\textperiodcentered}52; 1{\textperiodcentered}38-1{\textperiodcentered}67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts.

INTERPRETATION: Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes.

FUNDING: US National Kidney Foundation.

}, keywords = {Aged, Albuminuria, Cardiovascular Diseases, Cause of Death, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Risk Factors}, issn = {1474-547X}, doi = {10.1016/S0140-6736(12)61350-6}, author = {Fox, Caroline S and Matsushita, Kunihiro and Woodward, Mark and Bilo, Henk J G and Chalmers, John and Heerspink, Hiddo J Lambers and Lee, Brian J and Perkins, Robert M and Rossing, Peter and Sairenchi, Toshimi and Tonelli, Marcello and Vassalotti, Joseph A and Yamagishi, Kazumasa and Coresh, Josef and de Jong, Paul E and Wen, Chi-Pang and Nelson, Robert G} } @article {1385, title = {Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.}, journal = {JAMA}, volume = {307}, year = {2012}, month = {2012 May 09}, pages = {1941-51}, abstract = {

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking.

OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics.

DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged >= 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012.

MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years).

RESULTS: Estimated GFR was classified into 6 categories (>=90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4\% and 0.6\% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7\% to 6.3\%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7\% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95\% CI, 0.74-0.86) for all-cause mortality, 0.73 (95\% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95\% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and >=65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts.

CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

}, keywords = {African Continental Ancestry Group, Aged, Algorithms, Asian Continental Ancestry Group, Cardiovascular Diseases, Cohort Studies, Decision Support Techniques, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Models, Theoretical, Risk Assessment, Sex Factors}, issn = {1538-3598}, doi = {10.1001/jama.2012.3954}, author = {Matsushita, Kunihiro and Mahmoodi, Bakhtawar K and Woodward, Mark and Emberson, Jonathan R and Jafar, Tazeen H and Jee, Sun Ha and Polkinghorne, Kevan R and Shankar, Anoop and Smith, David H and Tonelli, Marcello and Warnock, David G and Wen, Chi-Pang and Coresh, Josef and Gansevoort, Ron T and Hemmelgarn, Brenda R and Levey, Andrew S} } @article {6797, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {591-601}, abstract = {

BACKGROUND: 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.

}, keywords = {Acute Kidney Injury, Adolescent, Adult, African Americans, Age Distribution, Aged, Albuminuria, Continental Population Groups, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Young Adult}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.337}, author = {Grams, Morgan E and Sang, Yingying and Ballew, Shoshana H and Gansevoort, Ron T and Kimm, Heejin and Kovesdy, Csaba P and Naimark, David and Oien, Cecilia and Smith, David H and Coresh, Josef and Sarnak, Mark J and Stengel, B{\'e}n{\'e}dicte and Tonelli, Marcello} }