Immune modulating therapy for IgA nephropathy: rationale and evidence

Our current understanding of the initial pathogenetic steps in IgA nephropathy (IgAN) provides relatively limited rationale for immunosuppressive therapy. However, it is conceivable that immunosuppressive drugs might affect secondary inflammatory events triggered by glomerular immune deposits or even proteinuria per se. Some, but not all, randomized clinical trials on either corticosteroid monotherapy, mycophenolate mofetil monotherapy, or immunosuppressive combination therapy have provided evidence for a benefit on either surrogate parameters such as proteinuria or hard end points such as renal failure. The central problem of these studies is that most were designed in the 1980s or 1990s, when recommendations for supportive therapy were strikingly different from those of today. In the meantime an equal number of randomized clinical studies reporting a benefit of supportive therapy has been published only regarding patients with IgAN and, unfortunately, no head-to-head comparisons of these 2 approaches currently are available. Several ongoing clinical trials may help to resolve this dilemma. Until the data of such studies become available, a pragmatic approach is to first optimize supportive therapy and reserve immunosuppressive medication for those patients failing a supportive approach and remaining at risk for progressive loss of renal function.