Proteinuria and Kidney Function Trajectories in Patients with Advanced CKD

KEY POINTS: Higher urine protein-to-creatinine ratios were strongly associated with a rapid decline in kidney function in patients with CKD stages G3b-G4. The stronger association observed with time-updated urine protein-to-creatinine ratio suggests that sustained lower urine protein-to-creatinine ratio was associated with lower risk of CKD progression. In advanced CKD, patients with lower proteinuria levels exhibited slower kidney function decline and longer time to eGFR threshold for kidney failure. BACKGROUND: Although 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 eGFR threshold in advanced CKD remains underexplored. METHODS: We analyzed 2727 participants with eGFR 15-45 ml/min per 1.73 m 2 without KRT from the Chronic Renal Insufficiency Cohort study and the Korean Cohort Study for Outcome in Patients with CKD (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 per 1.73 m 2 per year), whereas the exploratory outcome was projected time to reach the eGFR threshold of 10 ml/min per 1.73 m 2 for kidney failure. RESULTS: During 17,069 person-years of follow-up (median 4.9 years), the primary outcome occurred in 1474 participants (54%). Compared with UPCR <0.5 g/gCr, hazard ratios (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 to 2.45), 3.05 (2.64 to 3.52), and 6.32 (5.24 to 7.61), respectively. This association was stronger in analysis with time-updated UPCR, with the corresponding hazard ratios (95% CIs) of 2.58 (2.13 to 3.12), 5.61 (4.76 to 6.62), and 12.88 (10.58 to 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 per 1.73 m 2 per year. In addition, projected time to eGFR threshold for kidney failure (95% CIs) was lower progressively with increasing proteinuria categories, estimated at 28.7 (25.6 to 32.6), 10.3 (9.3 to 11.5), 6.4 (6.0 to 6.8), and 3.8 (3.5 to 4.2) years, respectively. CONCLUSIONS: Higher UPCRs 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.