Rationale & Objective: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. Study Design: Observational cohort study. Setting & Participants: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. Exposures: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. Outcomes: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. Analytical Approach: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. Results: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. Limitations: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. Conclusions: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.
American Journal of Kidney Diseases