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Decline in Estimated Glomerular Filtration Rate and Subsequent Risk of End-Stage Renal Disease and Mortality
Study Questions:
What is the association of decline in estimated glomerular filtration rate (eGFR) with subsequent progression to end-stage renal disease (ESRD) with implications for using lesser declines in eGFR as potential alternative endpoints for chronic kidney disease (CKD) progression?
Methods:
This was an individual 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 1-3 years and outcome data. Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis was conducted between July 2012 and September 2013, with baseline eGFR values collected from 1975 through 2012. The main outcomes measures were ESRD (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in eGFR over 2 years, adjusted for potential confounders and first eGFR.
Results:
The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger eGFR decline. Among participants with baseline eGFR of <60 ml/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% confidence interval [CI], 22.3-46.3) for changes of −57% in eGFR 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 (1-3 years), baseline eGFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline eGFR of 35 ml/min/1.73 m2) was 99% (95% CI, 95%-100%) for eGFR change of −57%, was 83% (95% CI, 71%-93%) for eGFR change of −40%, and was 64% (95% CI, 52%-77%) for eGFR change of −30% versus 18% (95% CI, 15%-22%) for eGFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) versus 32% (95% CI, 31%-33%), showing a similar but weaker pattern.
Conclusions:
The authors concluded that declines in eGFR smaller than a doubling of serum creatinine concentration occurred more commonly, and were strongly and consistently associated with the risk of ESRD and mortality.
Perspective:
This international meta-analysis of more than 1.7 million participants suggests that reductions in eGFR from baseline smaller than a doubling of serum creatinine concentration were strongly and consistently associated with subsequent risk of ESRD, and captured a much higher proportion of the subsequent ESRD risk, providing a basis for their use as alternative outcomes for CKD progression. The data support consideration of lesser declines in eGFR (such as a 30% reduction over 2 years) as an alternative endpoint for CKD progression. For clinical practice, the present analysis is useful for defining what level of change in the future may be considered important.
Keywords: Renal Dialysis, Prognosis, Kidney Failure, Chronic, Glomerular Filtration Rate, Confidence Intervals, Creatinine, Diabetes Mellitus
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