UACR And UPCR In CKD Trials: Kidney Failure Risk

Key Takeaways

• UACR AND UPCR were strongly associated with kidney failure, with UACR showing the stronger pooled association.
• The difference was clearest in type 2 diabetes and CKD and less clear in glomerular disease.

In a pooled analysis of four CKD trials, both UACR and UPCR were strongly associated with kidney failure, with a relative ratio of 1.10 favoring UACR. The dataset combined DAPA-CKD, EMPA-KIDNEY, RENAAL, and IDNT and included 6,219 participants with CKD, with and without diabetes. Investigators compared baseline urinary albumin-to-creatinine and protein-to-creatinine ratios rather than testing an intervention effect. In this pooled dataset, UACR showed the stronger association.

The article in Nephrology Dialysis Transplantation described a pooled individual participant-level analysis across DAPA-CKD, EMPA-KIDNEY, RENAAL, and IDNT. UACR and UPCR were derived from spot or 24-hour urine samples in participants with CKD, with and without diabetes. Kidney failure was defined as dialysis, transplantation, or sustained eGFR decline below 15 or below 10 mL/min/1.73 m2. Cox proportional hazards models were adjusted for demographic and clinical covariates, and results were pooled across trials with random-effects models. This allowed a direct comparison of how each urinary measure related to the same kidney outcome.

Across trials, the pooled hazard ratio per standard deviation increment in log-transformed UACR was 3.29, with a 95% confidence interval of 2.91 to 3.72. The corresponding pooled hazard ratio for log-transformed UPCR was 2.89, with a 95% confidence interval of 2.52 to 3.32. Investigators then compared these associations directly and reported an overall relative ratio of 1.10, with a 95% confidence interval of 1.03 to 1.18. This indicates a stronger association for UACR and does not indicate a treatment effect. The main quantitative comparison in the pooled analysis favored UACR overall.

Subgroup results showed the clearest difference in participants with type 2 diabetes and CKD, where the relative ratio was 1.12 with a 95% confidence interval of 1.04 to 1.20. In glomerular disease, the relative ratio was 0.97 with a 95% confidence interval of 0.83 to 1.13, indicating a less clear difference between the measures. The authors also noted that albuminuria is viewed as a sensitive predictor of kidney outcomes, while proteinuria remains in use because of cost considerations or tradition. They concluded that, with a standardized urinary albumin assay becoming clinically available in 2027, the pooled findings support UACR as the preferred urinary protein measure for risk stratification.