Proteinuria and Kidney Function Trajectories in Patients with Advanced CKD: Insights from CRIC and KNOW-CKD Studies.

INTRODUCTION: While urine protein-to-creatinine ratio (UPCR) is more commonly used than urine albumin-to-creatinine ratio in routine care, and particularly in low-resource settings; its association with kidney function decline and projected time to reach a kidney failure estimated glomerular filtration rate (eGFR) threshold in advanced chronic kidney disease (CKD) remains underexplored. METHODS: We analyzed 2,727 participants with eGFR 15-45mL/min/1.73 m2 without kidney replacement therapy (KRT) from the Chronic Renal Insufficiency Cohort (CRIC) study and the KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD). The main exposures were baseline and time-updated UPCR. The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of KRT. The secondary outcome was eGFR slope (mL/min/1.73 m2/year), whereas the exploratory outcome was projected time to reach the eGFR threshold of 10 mL/min/1.73 m2 for kidney failure. RESULTS: During 17,069 person-years of follow-up (median 4.9 years), the primary outcome occurred in 1,474 participants (54%). Compared with UPCR <0.5 g/gCr, hazard ratios (HRs) (95% confidence intervals [CIs]) for UPCR categories of 0.5-1.0, 1.0-3.0, and ≥ 3.0 g/gCr were 2.08 (1.76-2.45), 3.05 (2.64-3.52), and 6.32 (5.24-7.61), respectively. This association was stronger in analysis with time-updated UPCR, with the corresponding HRs (95% CIs) of 2.58 (2.13-3.12), 5.61 (4.76-6.62), and 12.88 (10.58-15.67), respectively. In secondary analyses, the eGFR slopes for the respective categories were -0.87 (-0.98 to -0.77), -2.32 (-2.56 to -2.07), -3.41 (-3.63 to -3.19), and -5.45 (-5.93 to -4.97) mL/min/1.73 m2 per year. Additionally, projected time to eGFR threshold for kidney failure (95% CIs) was lower progressively with increasing proteinuria categories, estimated at 28.7 (25.6-32.6), 10.3 (9.3-11.5), 6.4 (6.0-6.8), and 3.8 (3.5-4.2) years, respectively. CONCLUSIONS: Higher UPCR levels were strongly associated with accelerated CKD progression and shorter projected time to reach the eGFR threshold for kidney failure, underscoring the prognostic significance of proteinuria in patients with advanced CKD.