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ImportanceThe established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.ObjectiveTo characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.Data sources and study selectionIndividual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.Data extraction and synthesisTransfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.Main outcomes and measuresEnd-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.ResultsThe adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.Conclusions and relevanceDeclines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Evidence supports the use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) in patients with hypertension and stage 3 or milder chronic kidney disease (CKD). This systematic review and individual-level meta-analysis summarizes the evidence supporting the use of the medications in patients with hypertension and more advanced CKD. Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m 2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m 2 , of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. Primary Funding Source: National Institutes of Health. (PROSPERO: CRD42022307589) [ABSTRACT FROM AUTHOR]

BackgroundHigher urine albumin-creatinine ratio (ACR) is associated with cardiovascular disease (CVD) events, an association that is stronger than that between spot urine albumin on its own and CVD. Urine creatinine excretion is correlated with muscle mass, and low muscle mass also is associated with CVD. Whether low urine creatinine concentration in the denominator of the ACR contributes to the association of ACR with CVD is uncertain.Study designProspective cohort study.Setting & participants6,770 community-living individuals without CVD.PredictorsSpot urine albumin concentration, the reciprocal of the urine creatinine concentration (1/UCr), and ACR.OutcomeIncident CVD events.ResultsDuring a mean of 7.1 years of follow-up, 281 CVD events occurred. Geometric mean values for spot urine creatinine concentration, urine albumin concentration, and ACR were 95 ± 2 (SD) mg/dL, 0.7 ± 3.7 mg/dL, and 7.0 ± 3.1 mg/g. Urine creatinine concentration was lower in older, female, and low-weight individuals. Adjusted HRs per 2-fold higher increment in each urinary measure with CVD events were similar (1/UCr: 1.07 [95% CI, 0.94-1.22]; urine albumin concentration: 1.08 [95% CI, 1.01-1.14]; and ACR: 1.11 [95% CI, 1.04-1.18]). ACR ≥10 mg/g was associated more strongly with CVD events in individuals with low weight (HR for lowest vs highest tertile: 4.34 vs 1.97; P for interaction = 0.006). Low weight also modified the association of urine albumin concentration with CVD (P for interaction = 0.06), but 1/UCr did not (P for interaction = 0.9).LimitationsWe lacked 24-hour urine data.ConclusionsAlthough ACR is associated more strongly with CVD events in persons with low body weight, this association is not driven by differences in spot urine creatinine concentration. Overall, the associations of ACR with CVD events appear to be driven primarily by urine albumin concentration and less by urine creatinine concentration.

BackgroundAdding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined.MethodsWe performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C.ResultsIn the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR.ConclusionsThe use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).

BackgroundOften, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.MethodsWe utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System.ResultsOf 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR)

Background New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. Methods We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). Results Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. Conclusions In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions. [ABSTRACT FROM AUTHOR]

The commonly accepted glomerular filtration rate (GFR) threshold used to define chronic kidney disease is based on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. However, the appropriateness of the threshold in older adults is uncertain, partly because the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFR cr), which may be less accurate in older adults. This study evaluated associations between eGFR cr versus eGFR based on creatinine and cystatin C levels and 8 outcomes in older adults. Visual Abstract. Association of Low Glomerular Filtration Rate With Adverse Outcomes at Older Age in a Large Population With Routinely Measured Cystatin C: The commonly accepted glomerular filtration rate (GFR) threshold used to define chronic kidney disease is based on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. However, the appropriateness of the threshold in older adults is uncertain, partly because the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFR cr), which may be less accurate in older adults. This study evaluated associations between eGFR cr versus eGFR based on creatinine and cystatin C levels and 8 outcomes in older adults. Background: The commonly accepted threshold of glomerular filtration rate (GFR) to define chronic kidney disease (CKD) is less than 60 mL/min/1.73 m 2. This threshold is based partly on associations between estimated GFR (eGFR) and the frequency of adverse outcomes. The association is weaker in older adults, which has created disagreement about the appropriateness of the threshold for these persons. In addition, the studies measuring these associations included relatively few outcomes and estimated GFR on the basis of creatinine level (eGFR cr), which may be less accurate in older adults. Objective: To evaluate associations in older adults between eGFR cr versus eGFR based on creatinine and cystatin C levels (eGFR cr-cys) and 8 outcomes. Design: Population-based cohort study. Setting: Stockholm, Sweden, 2010 to 2019. Participants: 82 154 participants aged 65 years or older with outpatient creatinine and cystatin C testing. Measurements: Hazard ratios for all-cause mortality, cardiovascular mortality, and kidney failure with replacement therapy (KFRT); incidence rate ratios for recurrent hospitalizations, infection, myocardial infarction or stroke, heart failure, and acute kidney injury. Results: The associations between eGFR cr-cys and outcomes were monotonic, but most associations for eGFR cr were U-shaped. In addition, eGFR cr-cys was more strongly associated with outcomes than eGFR cr. For example, the adjusted hazard ratios for 60 versus 80 mL/min/1.73 m 2 for all-cause mortality were 1.2 (95% CI, 1.1 to 1.3) for eGFR cr-cys and 1.0 (CI, 0.9 to 1.0) for eGFR cr , and for KFRT they were 2.6 (CI, 1.2 to 5.8) and 1.4 (CI, 0.7 to 2.8), respectively. Similar findings were observed in subgroups, including those with a urinary albumin–creatinine ratio below 30 mg/g. Limitation: No GFR measurements. Conclusion: Compared with low eGFR cr in older patients, low eGFR cr-cys was more strongly associated with adverse outcomes and the associations were more uniform. Primary Funding Source: Swedish Research Council, National Institutes of Health, and Dutch Kidney Foundation. [ABSTRACT FROM AUTHOR]