Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy

Background. Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. Methods. We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 >= 2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of >= 30% decline in the estimated glomerular filtration rate or an increase in proteinuria >= 3.5 g/g during follow-up. Results. Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1-2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1-2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1-2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. Conclusions. Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.