Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality

Abstract

Importance: The 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.

Objective: To 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 selection: 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 to 3 years and outcome data.

Data extraction and synthesis: Transfer 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 measures: End-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.

Results: The 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 relevance: Declines 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.

Figure 1

Adjusted hazard ratio of end-stage renal disease associated with percent change in eGFR during a 2-year baseline period in eGFR<60 ml/min/1.73m² (A) and eGFR≥60 ml/min/1.73m² (B) and a histogram of the percent change in eGFR as well as approximate percent population attributable risk of end-stage renal disease. Values trimmed at <−70% change (0.22% and 0.055% of the study population in eGFR <60 and ≥60 ml/min/1.73m², respectively) and >40% change (5.9% and 0.51% of the population in eGFR <60 and ≥60 ml/min/1.73m², respectively).

Figure 2

Adjusted hazard ratio of all-cause mortality by percent change in eGFR, its distribution, and corresponding percent population attributable risk during a 2-year baseline period in eGFR<60 ml/min/1.73m² (A) and eGFR≥60 ml/min/1.73m² (B). Values trimmed at <−70% change (0.30% and 0.050% of the study population in eGFR <60 and ≥60 ml/min/1.73m², respectively) and >40% change (5.8% and 0.46% of the population in eGFR <60 and ≥60 ml/min/1.73m², respectively).