Predictive value of mesangial C3 and C4d deposition in IgA nephropathy
Authors
Ki Heon Nam ; Young Su Joo ; Changhyun Lee ; Sangmi Lee ; Joohwan Kim ; Hae-Ryong Yun ; Jung Tak Park ; Tae Ik Chang ; Dong-Ryeol Ryu ; Tae-Hyun Yoo ; Ho Jun Chin ; Shin-Wook Kang ; Hyeon Joo Jeong ; Beom Jin Lim ; Seung Hyeok Han ; Korean GlomeruloNEphritis sTudy (KoGNET) Group
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.