Association of C1q deposition with renal outcomes in IgA nephropathy

Background/Aims: IgA nephropathy (IgAN) is characterized by a highly variable clinical course. It has been reported that histopathologic lesions are risk factors for the progression of IgAN. The aim of this study was to investigate the relationships between co-deposition of C1q, clinicopathological features, and renal outcomes in patients with IgAN. Methods: This retrospective cohort study included 221 patients with primary IgAN who underwent renal biopsy at the Kyung Hee University Medical Center from January 1996 to December 2008. Patients were divided in two groups: Cl qpositive and C1q-negative. Using propensity scores to minimize confounding factors, we selected 36 matched C1q-negative patients from among the 203 unmatched C1q-negative patients and compared them with the 18 C1q-positive patients. We evaluated baseline characteristics and the severity of histologic lesions. We expressed the average rate of monthly renal function decline as the slope of eGFR (AGFR/M). Results: 18 patients with IgAN showed mesangial deposition of C1q (8.1%). The C1q-positive patients had higher mean systolic blood pressure values and more impaired renal function than the unmatched C1q-negative patients. However, this association was not seen when the Cl qpositive patients were compared with the matched C1q-negative patients. The slope of eGFR (AeGFR/M) declined steeply in the C1q-positive group. The incidence of severe cases of tubulointerstitial inflammation (TII) and fibrosis (TIP) was also greater in the C1q-positive group than the unmatched C1qnegative group, while only the incidence of severe TIP was significantly greater in the C1q-positive group than the matched Cl qnegative group. Biopsies from C1q-positive patients showed more intense IgA staining as well as positive rates of IgG and IgM staining than those of unmatched C1q-negative patients. However, compared with the matched C1q-negative group, only the IgG positive rate was significantly higher in the C1q-positive patients. Multiple regression analysis of C1q-positive and matched C1q-negative patients revealed that C1q deposition was a critical determinant of a poorer renal prognosis. Conclusions: Mesangial C1q deposition in the glomerulus is associated with a poor renal outcome and severe pathologic features in patients with IgAN. The deposition of C1q in IgAN could therefore serve as an indicator of a poor renal prognosis.