The Association of Proteinuria Target Achievement Timing and Stability with Adverse Kidney Outcomes Among Patients with IgA Nephropathy: A Cohort Study

Introduction: Current KDIGO guidelines for IgA nephropathy (IgAN) recommend proteinuria should be maintained at <0.5 g/day. In this study, we aim to evaluate the association of proteinuria target achievement timing and stability with adverse kidney outcomes. Methods: A cohort study was conducted with IgAN patients at Peking University First Hospital. We introduced three metrics: the timing of proteinuria first to target (TTT) in Part A, time in target range (TTR) and area out of target (AOT) of proteinuria in Part B to describe target achievement timing and stability respectively and the target of proteinuria was less than 0.5 g/day. We analyzed the association between those three metrics and the composite kidney outcome, which was defined as the first occurrence of either end-stage kidney disease (ESKD or a >50% decrease in eGFR from baseline. Results: In Part A, the primary outcome occurred in 166 (18.65%) patients. The 10-year kidney survival probability was 73% in TTT < 6 months group and 64% in TTT ≥ 6 months group (P=0.006). We identified a significant association between the rate of initial target achievement and clinical outcomes. In Part B, the primary outcome occurred in 385 (23.21%) patients. The 10-year kidney survival probability was 45% in T1 (TTR=0%); 60% in T2 (0%<TTR≤50%) and 86% in T3 (50%<TTR≤100%) groups (P<0.001). The corresponding HRs (95% CI) for the respective proteinuria-TTR categories were 0.54 (0.43-0.68), and 0.21 (0.15-0.31) respectively. Our results demonstrate that maintaining stable target-range duration strongly correlated with improved prognosis. Our further analysis using a restricted cubic spline model indicated that the association of TTR and primary outcome generally showed a linear relationship. The analysis of AOT showed consistent results. Conclusion: Our study supports the importance of rapidly reaching proteinuria remission (<6 months) and maintaining proteinuria within this target range for an extended period.