Proteinuria or Albuminuria as Markers of Kidney and Cardiovascular Disease Risk An Individual Patient–Level Meta-analysis

Background: Urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR) are both used in clinical practice to diagnose and monitor chronic kidney disease (CKD). Which measure exhibits stronger associations with clinical outcomes and whether this varies by patient characteristics are unknown. Objective: To assess and compare the performance of UACR and UPCR across CKD-related clinical outcomes. Design: Individual patient–level meta-analysis. Setting: 38 research and clinical cohorts. Participants: 148 994 participants with same-day measurements of UACR and UPCR. Measurements: We quantified the associations of UACR and UPCR with subsequent clinical outcomes, including kidney failure and cardiovascular events, using Cox proportional hazards regression. Analyses were done in each cohort, followed by random-effects meta-analysis. Subgroups included those based on severity of proteinuria, type 2 diabetes, estimated glomerular filtration rate (eGFR) less than 60 mL/min/ 1.73 m², and glomerular disease. Results: There were 148 994 participants and 9773 kidney failure events during a median of 3.8 years of follow-up. Higher UACR and UPCR both had a log-linear association with increased risk for kidney failure. The association with kidney failure was somewhat stronger for UACR (adjusted hazard ratio [HR] per SD increment, 2.55 [95% CI, 2.36 to 2.74]) than UPCR (HR, 2.40 [CI, 2.28 to 2.53]; P for comparison <0.001). Results were consistent to slightly stronger in subgroups with UACR greater than 30 mg/g, UPCR greater than 500 mg/g, eGFR less than 60 mL/min/1.73 m², diabetes, and glomerular disease. Associations between UACR and UPCR were generally similar for cardiovascular outcomes but favored UACR in subgroups with moderately to severely elevated UACR. Limitation: Assessment of UACR and UPCR in spot urine samples. Conclusion: Overall, UACR was more strongly associated with kidney failure than UPCR (particularly in subgroups with higher UACR), supporting the use of UACR rather than UPCR to diagnose and risk-stratify patients. Primary Funding Source: National Kidney Foundation and National Institute of Diabetes and Digestive and Kidney Diseases.