A large-scale meta-analysis provides further evidence supporting the use of early changes in albuminuria as a surrogate endpoint for kidney failure in clinical trials for chronic kidney disease (CKD).¹˒² The findings suggest that a reduction in urinary albumin:creatinine ratio (UACR) is strongly associated with a lower risk of long-term adverse kidney outcomes.
This individual participant data meta-analysis, conducted by the CKD-EPI Clinical Trials group, included 48 randomised controlled trials involving 85,681 participants.¹ The study was designed to evaluate the trial-level association between treatment effects on UACR change at 6 months and the established clinical endpoint. The primary composite endpoint was defined as kidney failure or a doubling of serum creatinine concentrations.
Across all included trials, the analysis demonstrated a significant correlation between changes in albuminuria and clinical outcomes. Each 30% reduction in the geometric mean of UACR in a treatment group, relative to a control group, was associated with an average 19% lower hazard for the primary clinical endpoint (95% Bayesian credible interval [BCI]: 5–30%).
The strength of this association was notable, with a median coefficient of determination (R²) of 0.66 (95% BCI: 0.06–0.98), indicating that changes in UACR explained a substantial portion of the treatment effect on the clinical endpoint. Furthermore, the investigators found no clear evidence that this association varied by the underlying aetiology of the CKD.
These results reinforce the value of albuminuria as a key biomarker in CKD management and research. By validating early UACR changes as a reliable surrogate for long-term kidney failure, these findings could help streamline and accelerate the development of new therapies. Using surrogate endpoints may allow for shorter and more efficient clinical trials, bringing potentially effective treatments to patients sooner. The authors concluded that these results provide further support for the use of albuminuria change as a surrogate endpoint in CKD clinical trials.¹
This study was funded by the National Kidney Foundation.
References
1. Heerspink HJL, Collier WH, Chaudhari J, et al. A meta-analysis of albuminuria as a surrogate endpoint for kidney failure. Nat Med (2025). https://doi.org/10.1038/s41591-025-04057-z
2. Heerspink HJL, et al. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019;7:128–139. https://doi.org/10.1016/S2213-8587(18)30314-0
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