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 aimed 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. 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 or a >50% decrease in estimated glomerular filtration rate 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 of group and 64% in TTT ≥6 months of 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 hazard ratios (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.