Caravaca-Fontán Fernando, Toledo-Rojas Remedios, Huerta Ana, Pérez-Canga José Luis, Martínez-Miguel Patricia, Miquel Rosa, Da Silva Iara, Verdalles Úrsula, Albornoz Macarena, Durán López Carmen Mercedes, Mon Carmen, Fernández-Juárez Gema, Praga Manuel
Department of Nephrology, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.
Department of Nephrology, Hospital Regional Universitario de Málaga, Málaga, Spain.
Kidney Int Rep. 2025 Jan 18;10(4):1223-1236. doi: 10.1016/j.ekir.2025.01.024. eCollection 2025 Apr.
C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases that share a similar pathogenesis; however, the prognostic significance of proteinuria reduction remains poorly characterized. This study compared the outcomes in C3G and IC-MPGN and assessed the impact of changes in proteinuria on kidney prognosis.
This retrospective, longitudinal, multicenter study used joint linear mixed-effects models to assess proteinuria trajectories, and Cox regression to evaluate their association with kidney failure. In addition, time-averaged proteinuria (TA-P) was calculated to determine its impact on kidney prognosis.
The study included 149 patients: 98 with C3G (66%) and 51 with IC-MPGN (34%) with a median age of 35 (interquartile range [IQR]: 22-53) years. During a median follow-up of 65 (IQR: 32-114) months, 44 patients (30%) progressed to kidney failure without differences across C3G or IC-MPGN. A strong association was observed between longitudinal increase in proteinuria and the risk of kidney failure. In addition, a ≥ 50% proteinuria reduction over time was associated with a lower risk of kidney failure (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.46-0.75, < 0.001). Results were consistent in both C3G and IC-MPGN, and in those with baseline estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m and proteinuria ≥ 1 g/d. A ≥30% proteinuria reduction at 6 months or a ≥50% proteinuria reduction at 12 months were associated with a slower eGFR decline. Patients were categorized into 4 subgroups based on TA-P levels, with TA-P values < 1 g/d indicating better kidney outcomes.
Proteinuria reduction was associated with improved kidney outcomes and slower eGFR decline in both C3G and IC-MPGN.
C3肾小球病（C3G）和原发性免疫复合物介导的膜增生性肾小球肾炎（IC-MPGN）是罕见疾病，具有相似的发病机制；然而，蛋白尿减少的预后意义仍未得到充分阐明。本研究比较了C3G和IC-MPGN的预后，并评估了蛋白尿变化对肾脏预后的影响。
这项回顾性、纵向、多中心研究使用联合线性混合效应模型评估蛋白尿轨迹，并使用Cox回归评估其与肾衰竭的关联。此外，计算时间平均蛋白尿（TA-P）以确定其对肾脏预后的影响。
该研究纳入了149例患者：98例C3G患者（66%）和51例IC-MPGN患者（34%），中位年龄为35岁（四分位间距[IQR]：22-53岁）。在中位随访65个月（IQR：32-114个月）期间，44例患者（30%）进展为肾衰竭，C3G或IC-MPGN之间无差异。观察到蛋白尿的纵向增加与肾衰竭风险之间存在密切关联。此外，随着时间推移蛋白尿减少≥50%与较低的肾衰竭风险相关（风险比[HR]：0.61；95%置信区间[CI]：0.46-0.75，P<0.001）。结果在C3G和IC-MPGN中均一致，在基线估计肾小球滤过率（eGFR）≥30 ml/min per 1.73 m²且蛋白尿≥1 g/d的患者中也一致。6个月时蛋白尿减少≥30%或12个月时蛋白尿减少≥50%与eGFR下降较慢相关。根据TA-P水平将患者分为4个亚组，TA-P值<1 g/d表明肾脏预后较好。
在C3G和IC-MPGN中，蛋白尿减少与改善的肾脏预后和较慢的eGFR下降相关。
