Clinical presentation, natural history, and treatment of crescentic proliferative IgA nephropathy.

IgA nephropathy is one of the most common causes of glomerulonephritis in the world and is characterized histologically by the deposition of polymeric forms of IgA within the mesangium and in some cases along the glomerular capillary wall.(1) Proliferative and crescenteric forms of IgA are associated with nephrotic range proteinuria, accelerated hypertension, and a more rapid decline toward end-stage renal disease. Previous attempts to categorize the incidence and clinical significance of proliferative IgA nephropathy have given conflicting results. This is in part the result of the lack of a uniform nomenclature and the failure of clinical therapies to prolong renal survival in specific subgroups. In the present study, we performed a prospective open-label trial of pulse solumedrol and intravenous cyclophosphamide in 20 patients with IgA nephropathy and at least 10% cellular crescents or endocapillary proliferation on renal biopsy. Seventeen patients underwent repeat kidney biopsies after 6 months of therapy, and the morphologic response to treatment was assessed using a modified systemic lupus erythematosis (SLE) histologic activity and chronicity index score. To determine the long-term efficacy of intravenous cyclophosphamide on renal survival, the results of the treated patients were compared with 12 untreated historical controls. Pulse solumedrol and intravenous cyclophosphamide effectively reduced peak serum creatinine, degree of proteinuria, the rate of decline in renal function, and the incidence of end-stage renal disease at 36 months.