A meta-analysis of albuminuria as a surrogate endpoint for kidney failure.

Abstract

Albuminuria is a central biomarker in chronic kidney disease (CKD), used for the detection and prognosis of the disease. In clinical trials assessing CKD progression, change in the level of albuminuria is a candidate surrogate endpoint for kidney failure. Evaluation of the validity of this surrogate endpoint across a diverse range of interventions and populations is required to support its further acceptance. Here, in an individual participant data analysis of 48 randomized controlled trials (studies) involving 85,681 participants, we assessed the association between treatment effects on 6-month urinary albumin:creatinine ratio (UACR) change and the established clinical endpoint of kidney failure or doubling of serum creatinine concentrations. Across all trials, each 30% reduction in the geometric mean of the UACR in the treatment group relative to the control group was associated with an average of 19% lower hazard for the clinical endpoint (95% Bayesian credible interval (BCI): 5-30%); median coefficient of determination (R²) = 0.66 (95% BCI: 0.06-0.98). There was no clear evidence that this association varied by CKD etiology. These results provide further support for use of albuminuria change as a surrogate endpoint in CKD clinical trials.