Time-Updated Estimated GFR Variability Is Associated With Mortality, Cardiovascular Disease, and End-Stage Kidney Disease in Patients With CKD: Findings From the CRIC Study.

Rationale & Objective: Previous reports have identified increased estimated glomerular filtration rate (eGFR) variability, measured during a single ascertainment window, as a risk factor for cardiovascular disease and all-cause mortality. We hypothesized that repeated measures of eGFR variability that are time-updated would exhibit stronger associations with common chronic kidney disease outcomes compared with eGFR variability derived from a single ascertainment window.

Study Design: Retrospective cohort study.

Setting & Participants: 4,224 participants in the Chronic Renal Insufficiency Cohort Study with an eGFR of 20-70mL/min/1.73m.

Exposure: Variability of eGFR was defined as the coefficient of variation calculated based on measures at 3 consecutive annual follow-up visits, starting at baseline and time-updated repeatedly in 1-year sliding windows.

Outcome: Cardiovascular disease, end-stage kidney disease, and death.

Analytical Approach: Cox proportional hazards models that included baseline covariates and eGFR variability measured during the first ascertainment window (baseline model) and marginal structural models that included repeated measures of eGFR variability and covariates (time-updated model).

Results: In the baseline and time-updated multivariable adjusted analyses, each standard deviation increase in eGFR rate variability was associated with a respective 1.04-fold (95% CI, 0.96-1.13) and 3.34-fold (95% CI, 2.33-4.79) increased risk of cardiovascular disease, 1.08-fold (95% CI, 0.99-1.18) and 5.97-fold (95% CI, 3.74-9.52) increased risk of end-stage kidney disease, and 1.15-fold (95% CI, 1.08-1.23) and 1.52-fold (95% CI, 1.19-1.94) increased risk of all-cause mortality.

Limitations: Residual confounding and differences in eGFR intervals from real-world clinical practice.

Conclusions: Variability in eGFR over time is independently associated with risks of cardiovascular and kidney outcomes and mortality, even after accounting for the absolute level of eGFR and eGFR slope.

Plain-language Summary: Estimated glomerular filtration rate (eGFR) is a key indicator of kidney function calculated from routine clinical blood test results. It is well established that variability in eGFR over time is associated with poor patient outcomes such as mortality. However, previous analyses have primarily focused on the relationship between the initial eGFR variability observed and future adverse events. In this study, we continuously updated eGFR variability over time and analyzed its association with the development of cardiovascular disease, end-stage kidney disease, and mortality. Our findings demonstrated a stronger association between time-updated eGFR variability and these outcomes compared with the previous analytical methods.