目的:蛋白尿是预测IgA肾病(IgAN)长期肾脏结局的替代终点,其水平<1g/d被确定为治疗目标。然而,这个门槛还没有得到充分的研究。我们旨在量化IgAN进展与各种蛋白尿水平的相关性。
方法:观察性队列研究。
方法:&研究对象:1530例IgAN患者,在北京大学第一医院进行至少12个月的随访。
方法:蛋白尿水平随时间更新(TV-P)。
结果:eGFR或终末期肾病(ESKD)降低50%的复合肾脏结局。
方法:边缘结构模型(MSM)。
结果:中位随访43.5[27.2,72.8]个月后,254例(16.6%)患者出现了复合肾脏结局。在蛋白尿≥0.5g/d的患者中,TV-P与风险较高的复合肾脏结局之间存在分级关联。与TV-P<0.3g/d相比,蛋白尿水平为0.3-<0.5g/d的HR(95%CI),0.5-<1.0g/d,1.0-<2.0g/d和≥2.0g/d分别为2.22(0.88-5.58),4.04(1.93-8.46),8.46(3.80-18.83)和38.00(17.62-81.95),分别。在基线蛋白尿≥1.0g/d的患者中,与TV-P<0.3g/d相比,TV-P为0.3至<0.5g/d的风险更高(HR3.26,95%CI1.07-9.92;P=0.04)。然而,在基线蛋白尿水平<1g/d的患者中,当TV-P≥1.0g/d时,复合肾脏结局的风险才开始增加(HR3.25,95%CI1.06-9.90).
结论:单中心观察性研究,选择偏倚和未测量的混杂因素结论:这项研究表明,IgAN和蛋白尿水平>0.5g/d的患者,肾衰竭的风险升高,尤其是在开始治疗前蛋白尿水平≥1.0g/d的患者中。这些数据可用于告知在IgAN的治疗中蛋白尿靶标的选择。
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], P=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.