We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

中文翻译：

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肾小球系膜C3和C4d沉积在IgA肾病中的预测价值。

我们旨在确定每个补体（C3和C4d）沉积对IgA肾病（IgAN）进展的相对贡献。我们总共招募了380例经活检证实的IgAN的患者。通过免疫荧光染色和免疫组织化学分别评估C3（<2+ vs.≥2+）和C4d（阳性与阴性）的肾小球系膜沉积。研究终点是eGFR或ESRD下降30％的综合结果。C3≥2+和C4d（+）的患者达到主要结局的风险明显高于相应的患者。将C3沉积物添加到肾脏活检中获得的临床数据中，会适度增加接收者操作特征曲线下的面积，改善净重分类和改善综合辨别力（IDI）；添加C4d仅增加了IDI。综上所述，肾小球系膜C3和C4d沉积是IgAN进展的独立危险因素。C3显示出比C4d更好的可预测性，表明仅凝集素途径具有有限的临床预后价值。