Treatment of IgA nephropathy: Recent advances and prospects

Abstract

IgA nephropathy, identified 50 years ago in France, is the most frequent glomerular disease worldwide. The course is variable, but in most of the cases there is a relentless decline in renal function, reaching end-stage renal failure in 10-60% of the cases after 10 years and in 40% after 20 years. These data justify the interest for finding a suitable therapeutic approach particularly in progressive cases. A supportive care, including renin-angiotensin system inhibitors is the priority in cases with slowly declining renal function, particularly when developing proteinuria. The recent supportive versus immunosuppressive therapy for the treatment of progressive IgA nephropathy (STOP-IgAN) randomized and controlled trial has further stressed the benefit of a strict supportive care including also life-style changes, protein and salt restriction. However, there is clear evidence from observational studies (including the European Validation Study of the Oxford Classification of IgA nephropathy [VALIGA]) and a new randomized and controlled trial (Therapeutic Evaluation of Steroids in IgA Nephropathy Global [TESTING]) of additional benefits of corticosteroid treatment in patients with proteinuric IgA nephropathy. However, the present treatment schedules carry severe side effects, mostly infectious complications, which indicate the need for less toxic interventions. The recent focus on the role of gut-kidney axis in IgA nephropathy has led to the search of corticosteroid formulations targeting the intestinal mucosal immune system (gut-associated lymphoid tissue). The NEFIGAN trial obtained interesting results in terms of reduction of proteinuria and stabilization of renal function using a budesonide formulation allowing a selective drug delivery at intestinal gut-associated lymphoid tissue sites. The adverse events, particularly infections, were found to be not clinically relevant. The possibility of a personalized approach to the treatment according to the renal biopsy lesions (Oxford MEST score) is supported by several uncontrolled studies and deserves great attention in the next future. New treatments options for IgA nephropathy include drugs targeting BAFF, a B-cell factor crucial for IgA synthesis or targeting the complement system, and also the possibility of acting directly on the deposited IgA by selective protease digestion.

Keywords: Corticosteroids; IgA nephropathy; Immunosuppressors; Risk factors for progression; Treatment.