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Time-Varying Proteinuria and Progression of IgA Nephropathy: A Cohort Study
American Journal of Kidney Diseases ( IF 13.2 ) Pub Date : 2024-02-15 , DOI: 10.1053/j.ajkd.2023.12.016 Chen Tang , Pei Chen , Feng-Lei Si , Ji-Cheng Lv , Su-Fang Shi , Xu-Jie Zhou , Li-Jun Liu , Hong Zhang
American Journal of Kidney Diseases ( IF 13.2 ) Pub Date : 2024-02-15 , DOI: 10.1053/j.ajkd.2023.12.016 Chen Tang , Pei Chen , Feng-Lei Si , Ji-Cheng Lv , Su-Fang Shi , Xu-Jie Zhou , Li-Jun Liu , Hong Zhang
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Proteinuria is a surrogate end point for predicting long-term kidney outcomes in IgA nephropathy (IgAN) with levels<1g/day identified as a therapeutic target. However, this threshold has not been sufficiently studied. We quantified the associations of progression of IgAN with various levels of proteinuria. Observational cohort study. 1,530 patients with IgAN and at least 12 months of follow-up at Peking University First Hospital. Proteinuria levels updated over time (time-varying proteinuria, TVP). A composite kidney outcome of a 50% reduction in the estimated glomerular filtration rate or end-stage kidney disease. Marginal structural models. After a median follow-up period of 43.5 (IQR, 27.2-72.8) months, 254 patients (16.6%) developed the composite kidney outcome. A graded association was observed between TVP and composite kidney outcomes with higher risk among those with proteinuria of≥0.5g/day. Compared with TVP<0.3g/day, the HRs for proteinuria levels of 0.3 to<0.5g/day, 0.5 to<1.0g/day, 1.0 to<2.0g/day, and≥2.0g/day were 2.22 (95% CI, 0.88-5.58), 4.04 (95% CI, 1.93-8.46), 8.46 (95% CI, 3.80-18.83), and 38.00 (95% CI, 17.62-81.95), respectively. The trend was more pronounced in patients with baseline proteinuria of≥1.0g/day, among whom a higher risk was observed with TVP of 0.3 to<0.5g/day compared with TVP<0.3g/day (HR, 3.26 [95% CI, 1.07-9.92], =0.04). However, in patients with baseline proteinuria levels of<1g/day, the risk of composite kidney outcome only began to increase when TVP was≥1.0g/day (HR, 3.25 [95% CI, 1.06-9.90]). Single-center observational study, selection bias, and unmeasured confounders. This study showed that patients with IgAN and proteinuria levels of>0.5g/day, have an elevated risk of kidney failure especially among patients with proteinuria levels≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN. The presence of proteinuria has often been considered a surrogate end point and a possible therapeutic target in clinical trials in IgA nephropathy (IgAN). Some guidelines recommend a reduction in proteinuria to<1g/day as a treatment goal based on the results of previous longitudinal studies. However, these findings may have been biased because they did not properly adjust for time-dependent confounders. Using marginal structural models to appropriately account for these confounding influences, we observed that patients with IgAN and proteinuria levels≥0.5g/day have an elevated risk of kidney failure, especially among patients who had proteinuria levels of≥1.0g/day before initiating treatment. These data may serve to inform the selection of proteinuria targets in the treatment of IgAN.
更新日期：2024-02-15
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