Abstract: TH-OR085
Albuminuria Change as a Surrogate End Point for Kidney Failure: An Updated Meta-Analysis of Randomised Controlled Trials
Session Information
- Late-Breaking Research Orals - 1
November 06, 2025 | Location: Grand Ballroom C, Convention Center
Abstract Time: 04:42 PM - 04:54 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Heerspink, Hiddo Jan L., Rijksuniversiteit Groningen, Groningen, GR, Netherlands
- Collier, Willem H., The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Greene, Tom, The University of Utah School of Medicine, Salt Lake City, Utah, United States
- Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
Group or Team Name
- CKD-EPI Clinical Trials Consortium.
Background
Albuminuria change is a candidate surrogate endpoint for kidney failure in clinical trials of chronic kidney disease (CKD) progression. Understanding its validity across a diverse range of interventions and populations is required to support its further acceptance as surrogate endpoint.
Methods
We performed an individual participant data analysis of 48 randomized controlled trials (studies) involving 85,681 participants with baseline urine albumin-to-creatinine ratio (UACR) >30 mg/g of whom 12335 (14.4%) had CKD of unspecified cause, 72,309 (84.4%) had diabetes, and 1037 (1.2%) had IgA nephropathy. We assessed the association between treatment effects on 6-month UACR change and the established kidney endpoint of kidney failure or doubling of serum creatinine using Bayesian meta-regression models.
Results
Across all studies, each 30% reduction in geometric mean UACR by the treatment relative to control was associated with an average 19% lower hazard for the clinical endpoint [95% Bayesian Credible Interval (BCI) 5%, 30%]; median R2=0.66 [95% BCI 0.06, 0.98]. There was no evidence that this association varied by CKD aetiology (Table 1). The model predicted a probability of clinical benefit of at least 97.5% when the observed treatment effect on UACR is 27% in a study of 200 participants.
Conclusion
These results provide further support for use of albuminuria change as a surrogate endpoint in CKD clinical trials.
Table 1: Trial level association between treatment effects on UACR and the treatment effects on the clinical endpoint
| N Studies | Meta-regression slope (95% BCI) | Intercept (95% BCI) | R2 (95% BCI) | RMSE (95% BCI) | |
| Overall | 48 | 0.68 (0.17, 1.19) | -0.05 (-0.22, 0.11) | 0.66 (0.06, 0.98) | 0.08 (0.02, 0.17) |
| Diabetes | 18 | 0.65 (0.03, 1.27) | -0.02 (-0.22, 0.18) | 0.72 (0.02, 1.00) | 0.06 (0.00, 0.18) |
| CKD* | 23 | 0.66 (-0.01, 1.34 | -0.10 (-0.32, 0.11) | 0.85 (0.03, 1.00) | 0.04 (0.00, 0.17) |
| IgAN | 7 | 1.35 (0.28, 3.05) | -0.18 (-0.72, 0.22) | 0.98 (0.08, 1.00) | 0.05 (0.00, 0.61) |
*Chronic Kidney Disease of unspecified cause; Abbreviations: CKD, chronic kidney disease; IgA, Immunoglobin A Nephropathy; RMSE, root mean square error
Funding
- Private Foundation Support