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Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

ABSTRACT: BACKGROUND:The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. METHODS:We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. FINDINGS:The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. INTERPRETATION:Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. FUNDING:US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.

SUBMITTER: Matsushita K

PROVIDER: S-EPMC4594193 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

Matsushita Kunihiro K Coresh Josef J Sang Yingying Y Chalmers John J Fox Caroline C Guallar Eliseo E Jafar Tazeen T Jassal Simerjot K SK Landman Gijs W D GW Muntner Paul P Roderick Paul P Sairenchi Toshimi T Schöttker Ben B Shankar Anoop A Shlipak Michael M Tonelli Marcello M Townend Jonathan J van Zuilen Arjan A Yamagishi Kazumasa K Yamashita Kentaro K Gansevoort Ron R Sarnak Mark M Warnock David G DG Woodward Mark M Ärnlöv Johan J

The lancet. Diabetes & endocrinology 20150528 7

<h4>Background</h4>The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach.<h4>Methods</h4>We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) i ...[more]

PMID: 26028594

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Project description:ImportanceChronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.ObjectiveTo evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.Design, setting, and participantsIndividual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.ExposuresThe Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR).Main outcomes and measuresThe risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses.ResultsWithin the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]).Conclusions and relevanceIn this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Project description:BACKGROUND:Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS:In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS:The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION:eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING:Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.

Project description:ObjectiveTo assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.DesignRandom effects meta-analysis using pooled individual participant data.Setting46 cohorts from Europe, North and South America, Asia, and Australasia.Participants2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g).ResultsRisks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.ConclusionsBoth sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

Project description:BackgroundClassification of chronic kidney disease (CKD) and evaluation of prognosis is based on two components: estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). In multiethnic populations, ethnic-specific discrepancies in both parameters may exist. It is unknown whether variations in CKD risk factors may explain these discrepancies.MethodsWe cross-sectionally analyzed baseline eGFR (CKD-EPI formula) and ACR of 21,421 participants (aged 18-70 years) of the HELIUS cohort who were randomly sampled between 2011 and 2015, stratified by ethnicity, through the municipality register of Amsterdam. Six ethnic groups were distinguished, including participants of Dutch (4539), South-Asian Surinamese (3027), African Surinamese (4114), Ghanaian (2297), Turkish (3576) and Moroccan (3868) descent. Multiple regression analyses to determine ethnic differences were performed, with additional adjustments for age, sex, traditional cardiovascular and renal risk factors, and adjustment for level of education.FindingsMean (SE) eGFR was higher in all ethnic minority groups as compared to Dutch participants (eGFR 94.7 ± 0.3 mL/min/1.73 m2) with age- and sex-adjusted differences ranging from 1.5 ± 0.30 in South-Asian Surinamese to 10.1 ± 0.28 mL/min/1.73 m2 in Moroccan participants. ACR was higher in ethnic minority groups as compared to Dutch participants (ACR 0.64 ± 0.20 mg/mmol), with age- and sex-adjusted differences ranging from 0.46 ± 0.20 in African Surinamese participants to 1.70 ± 0.21 mg/mmol in South-Asian Surinamese participants. Differences in both parameters diminished after multiple adjustments, but remained highly significant.InterpretationBoth eGFR and ACR are higher among ethnic minority groups as compared to individuals of Dutch origin-independent of age, sex, prevalence of traditional cardiovascular and renal risk factors, and parameters of socioeconomic status. Future studies should address the potential uncertainty in predicting CKD and CKD-related complications when using both parameters in ethnically diverse populations. Also, identification of driving factors leading to these discrepancies might contribute to improved population screening for CKD.FundingThe HELIUS study is conducted by the Amsterdam University Medical Center and the Public Health Service of Amsterdam. Both organizations provided core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation (2010T084), the Netherlands Organization for Health Research and Development (ZonMw: 200500003), the European Union (FP7: 278901), and the European Fund for the Integration of non-EU immigrants (EIF: 2013EIF013).

Project description:Background and objectivesExposure to particulate matter (PM) <2.5 μm in aerodynamic diameter (PM2.5) has been linked to detrimental health effects. This study aimed to describe the relationship between long-term PM2.5 exposure and kidney disease, including eGFR, level of albuminuria, and incident CKD.Design, setting, participants, & measurementsThe study included 10,997 participants from the Atherosclerosis Risk in Communities cohort who were followed from 1996-1998 through 2016. Monthly mean PM2.5 concentrations (μg/m3) were estimated at geocoded participant addresses using geographic information system-based, spatiotemporal generalized additive mixed models-including geospatial covariates such as land use-and then averaged over the 12-month period preceding participant examination. Covariate-adjusted, cross-sectional associations of PM2.5, baseline eGFR, and urinary albumin-creatinine ratio (UACR) were estimated using linear regression. PM2.5 and incident CKD (defined as follow-up eGFR <60 ml/min per 1.73 m2 with ≥25% eGFR decline relative to baseline, CKD-related hospitalization or death based on International Classification of Diseases 9/10 codes, or development of ESKD) associations were estimated using Cox proportional hazards regression. Modeling was stratified by study site, and stratum-specific estimates were combined using random-effects meta-analyses.ResultsBaseline mean participant age was 63 (±6) years and eGFR was 86 (±16) ml/min per 1.73 m2. There was no significant PM2.5-eGFR association at baseline. Each 1-μg/m3 higher annual average PM2.5 was associated with higher UACR after adjusting for demographics, socioeconomic status, and clinical covariates (percentage difference, 6.6%; 95% confidence interval [95% CI], 2.6% to 10.7%). Each 1-μg/m3 higher annual average PM2.5 was associated with a significantly higher risk of incident CKD (hazard ratio, 1.05; 95% CI, 1.01 to 1.10).ConclusionsExposure to higher annual average PM2.5 concentrations was associated with a higher level of albuminuria and higher risk for incident CKD in a community-based cohort.

Dataset Information

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

Publications

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

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