Urinary protein vs albumin for assessing kidney failure risk in chronic kidney disease

The urinary albumin-to-creatinine ratio (UACR) is an established surrogate endpoint for kidney failure in chronic kidney disease (CKD). However, proteinuria remains widely used in routine clinical practice in several countries due to its accessibility and cost-effectiveness. Moreover, the comparative utility of UACR and proteinuria as surrogate endpoints is not well-defined.

We analyzed data from the Chronic Kidney Disease Japan Cohort to examine the association between a 30% decrease in urinary protein-to-creatinine ratio (UPCR) or UACR over 2 years and the subsequent risk of kidney failure requiring replacement therapy (KFRT). We also examined the relationship between a 30% decrease in UPCR over 1 year and the risk of KFRT. Associations were evaluated using multivariable Cox proportional hazards models.

Among the 2966 patients, 603 had both UACR and UPCR data available over 2 years. Their mean age was 60 years, mean estimated glomerular filtration rate (eGFR) was 29 ml/min/1.73 m², median UPCR was 0.81 g/gCr, and median UACR was 601 mg/gCr. During a median follow-up of 4.9 years, 245 patients (40.6%) progressed to KFRT. A 30% decrease in UPCR over 2 years was significantly associated with a lower risk of KFRT [hazard ratio (HR), 0.52 (0.38, 0.71)], with comparable findings for UACR [HR, 0.58 (0.41, 0.82)]. A similar association was observed for UPCR over 1 year among 831 patients [HR 0.56 (0.43, 0.73)]. Subgroup analyses showed consistent associations across most baseline characteristics. Nevertheless, the association of UPCR change was weaker than that of UACR change in patients with eGFR < 15 ml/min/1.73 m², possibly reflecting the reduced urinary albumin-to-protein ratio.

In patients with CKD, a 30% decrease in UPCR or UACR over 2 years may serve as a comparable surrogate endpoint for subsequent KFRT. Nonetheless, caution is warranted in patients with eGFR < 15 ml/min/1.73 m².