Comparison of Urine Albumin-to-Creatinine Ratio (UACR) and Protein-to-Creatinine Ratio (UPCR) as Markers of Kidney and Cardiovascular Disease Risk: A Multinational, Patient-Level Meta-Analysis

Background: Urinary albumin:creatinine ratio (UACR) and protein:creatinine ratio (UPCR) are used clinically to diagnose and monitor chronic kidney disease (CKD). Which measure exhibits the stronger association with clinical outcomes, and whether this varies by patient characteristics has only been evaluated in relatively small studies. Our aim was to assess and compare UACR and UPCR performance across CKD-related clinical outcomes. Methods: Individual patient-level meta-analysis of 37 research and clinical cohorts with same-day measures of UACR and UPCR were included. We quantified the associations of each standard deviation (SD) increment in UACR and UPCR with subsequent clinical outcomes, including kidney failure with kidney replacement therapy, heart failure, myocardial infarction, stroke and cardiovascular death, using Cox regression adjusted for demographic and clinical covariates. Analyses were performed in each cohort, followed by random-effects meta-analysis. A priori subgroups included severity of proteinuria, type 2 diabetes, eGFR <60 mL/min/1.73m2, and glomerular disease. Results: Among 148,994 individuals followed for a median of 3.8 years, 9,773 kidney failure events occurred.Higher UACR and UPCR were both log-linearly associated with increased risk of kidney failure. The meta-analyzed association with kidney failure was somewhat stronger for UACR (multivariable adjusted hazard ratio (HR) per SD increment 2.54 [95%CI 2.36, 2.74]) compared with UPCR (HR 2.39 [95%CI 2.28, 2.52]; p<0.001). Adjusted HRs remained higher for UACR compared to UPCR among people with UACR >30 mg/g, UPCR >500 mg/g, eGFR <60 mL/min/1.73m2, diabetes, and glomerular disease. Superiority of UACR was more pronounced in those with moderate-severe proteinuria (HR 2.92 [2.52, 3.39] for UACR vs. 2.54 [2.35, 2.75] for UPCR; p<0.001). Associations between UACR and UPCR were similar for cardiovascular outcomes but favoured UACR in those with moderate-severe proteinuria. Conclusion: Both UACR and UPCR are strong predictors of kidney and cardiovascular outcomes. UACR was more strongly associated with kidney failure, particularly in subgroups with higher risk. Given impending global standardization of UACR assays, this data supports use of UACR as the preferred measure of proteinuria to diagnose and risk-stratify patients. Funding: NIDDK Support, Private Foundation Support