Present and future therapy options in IgA-nephropathy

Over the last 5 years the evidence base for therapeutic approaches in patients at risk for progressive IgA-nephropathy (IgAN) has markedly improved. In addition to several studies with low power, two randomized controlled trials suggest that in patients with preserved renal function, i.e. a GFR above 70 ml/min, corticosteroid-therapy can effectively prevent the development of progressive renal failure, whereas in patients with already impaired renal function, combination therapy consisting of cyclophosphamide, azathioprine and corticosteroids was effective. However, so far no study has firmly established that such immunosuppressive therapy is indeed superior to aggressive supportive therapy as it is available nowadays, i.e. high dose ACE-inhibitors and/or angiotensin-II receptor blockers, smoking cessation etc. It therefore appears prudent to first institute such supportive therapy and to limit immunosuppressive therapy to those patients, who maintain a proteinuria above 1 g/day or exhibit a progressive decline of GFR despite optimal supportive measures. Based on pathogenetic insights derived from experimental studies, antagonism of platelet-derived growth factor-B or -D provides an attractive and possibly more specific therapeutical alternative to immunosuppression. While clinical studies testing this new approach are about to start, the development of other novel therapeutic approaches is greatly hampered by the lack of sufficient animal models of IgAN. In this respect a recently described primate model of IgAN offers some hope for the future.