Rapidly progressive IgA nephropathy: a form of vasculitis or a complement-mediated disease?

Abstract

A rapidly progressive and crescentic IgA nephropathy (IgAN) is uncommon, but it has a high risk of progression to end-stage renal disease and variable response to immunosuppression. The importance of a positive anti-neutrophil cytoplasmic antibody (ANCA) serology in this group of patients is not fully understood but may have prognostic significance. On the other hand, there is growing evidence of the role of complement in the pathogenesis of IgAN, especially in cases of crescentic IgAN. Therapies directed against the complement system are a potential and rational therapeutic approach. In this issue, two clinical studies of crescentic IgAN are presented. The first work, is a retrospective case-control study describing clinical presentation, histological findings and response to treatment of crescentic IgAN/positive ANCA patients, comparing them with IgAN/negative ANCA patients and ANCA vasculitis patients. The second is a case report showing the effect of eculizumab, a humanized monoclonal antibody that is a terminal cascade complement inhibitor, as salvage therapy for crescentic IgAN resistant to conventional immunosuppression. Both studies broaden our approach to patients with aggressive forms of IgAN.

Keywords: ANCA; IgA nephropathy; complement activation; crescentic glomerulonephritis.

Fig. 1.

Main pathogenic mechanisms involved in renal damage in IgA nephropathy. IgA, immunoglobulin A; IC, immune complex; PR3, proteinase-3; MPO, myeloperoxidase.

Fig. 2.

Current therapeutic alternatives for crescentic IgA nephropathy. ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; CS, corticosteroids; IgA, immunoglobulin A nephropathy; MMF, mycophenolate mofetil; PE, plasma exchange; RTX, rituximab.