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Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

ABSTRACT: Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m(2) but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.

SUBMITTER: Gansevoort RT

PROVIDER: S-EPMC3959732 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

Gansevoort Ron T RT Matsushita Kunihiro K van der Velde Marije M Astor Brad C BC Woodward Mark M Levey Andrew S AS de Jong Paul E PE Coresh Josef J

Kidney international 20110202 1

Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at v ...[more]

PMID: 21289597

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Project description:Rationale & objectiveDetermining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease.Study designCross-sectional study with multiple collections over less than 4 weeks.Setting & participantsClinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g).ExposureRepeat measurements from serially collected samples across 3 study visits.OutcomesMeasurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β2-microglobulin (B2M), and beta trace protein (BTP).Analytical approachWe calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.ResultsMedian CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values.LimitationsSmall sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.ConclusionseGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.

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:Rationale & objectiveThere are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status.Study designMeta-analysis.Study populationsAdults with type 2 diabetes, chronic kidney disease, or heart failure.Selection criteria for studiesRandomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events.Data extractionPublications of 10 trials to November 20, 2020.Analytical approachThe incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups.ResultsSubgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of <45, 45 to <60, and ≥60 mL/min/1.73 m2, reduced 16.0, 9.5, and 1.9 heart failure events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity). In urine UACR subgroups of >300, 30 to 300, and <30 mg/g, SGLT2 inhibitors reduced 17.3, 1.4, and 2.2 kidney disease events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity), and 14.8, 8.7, and 2.1 heart failure events per 1,000 patient-year, respectively (P = 0.006 for heterogeneity). The pooled IRDs for major cardiovascular events were also greater in lower eGFR or overt albuminuria subgroups. In secondary analyses, risk differences calculated using pooled baseline and relative risks were comparable to the pooled IRDs, while the relative risk reductions for kidney and heart failure outcomes were consistent across the subgroups. For treatment-related harms, IRDs were similar between eGFR subgroups.LimitationsStudy-level data rather than individual patient data were used.ConclusionsSGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts.

Dataset Information

Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

Publications

Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

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