Association of UACR and UPCR with kidney failure: analysis of observational data in patients with rare kidney diseases

BACKGROUND: Proteinuria is associated with long-term kidney failure (KF) risk. In trials of CKD and diabetic kidney disease, urine albumin:creatinine ratio (ACR) has been the preferred urinary protein measurement and features in guidelines and risk-prediction models. In studies of rare, glomerular diseases, urine protein: creatinine ratio (PCR) has more often been used, consequently featuring in treatment algorithms for these diseases. While equations estimating ACR from PCR (estACR) have been developed in large CKD cohorts, whether ACR, PCR, non-albumin proteinuria, and estACR differ in their relationships with KF in patients with rare kidney diseases is unknown. METHODS: Patients in RaDaR with same-day ACR and PCR measurements were included. Analyses were undertaken for the whole cohort, and by disease subtype and ACR tertile. Calibration plots assessed the performance of converting PCR to ACR. Cox regression models of time to KF or death (adjusting for age, sex, eGFR, disease) were run with four proteinuria measures: ACR, PCR, non-albumin proteinuria and estACR. Model fit was assessed using AIC (Akaike information criterion) and SBC (Schwarz Bayesian information Criterion) values, ROC curves and time-dependent AUC, and concordance compared using Uno's C statistic. RESULTS: Out of 4156 patients, 717 (17%) experienced a KF or death event. At lower predicted ACR deciles, conversion of PCR to ACR underestimated true ACR. Very similar AIC and SBC statistics were observed for all proteinuria measurements, including estACR. Time-dependent AUC at 5 years were >0.83 for all models and disease sub-groups. No statistically significant differences in model concordance were seen (Chi2 P > .2 for all comparisons). Within each ACR tertile, AIC, SBC, and AUC values were similar across all proteinuria metrics. CONCLUSIONS: In this cohort of patients with rare kidney diseases, across all levels of proteinuria studied, we identified no statistically significant differences in the performance of ACR, PCR, non-albumin proteinuria, or estACR to predict KF risk.