Standard immunosuppressive therapy of immune-mediated glomerular diseases

Glomerulonephritis (GN) accounts for 10%-20% of the total incident cases of end stage renal disease (ESRD), and is the third most common cause of ESRD after diabetes and hypertension in western countries. The pathogenesis of glomerulonephritis is prevalently immune mediated: humoral and cell-mediated immunity are involved, although the rationale for an etiological treatment is still lacking. In the last forty years, empirical treatment based upon the use of corticosteroids and/or immunosuppressive drugs have obtained excellent results in improving survival of both the patient and the kidney. Almost 95% of children affected by minimal change disease (MCD) achieve remission of proteinuria within 4 to 8weeks of prednisone administration. In adults with focal segmental glomerulosclerosis (FSGS), prednisone induces complete or partial remission in the majority of patients, but a longer period of steroid treatment or the combination of calcineurin inhibitors or cytotoxic drugs can be needed. A percentage of 65%-70% of patients with idiopathic membranous nephropathy (MN) reach complete or partial remission with a 6-month course of therapy alternating glucocorticoids with alkylating agents. Glucocorticoids plus cyclophosphamide, and, on occasion, plasmapheresis are effective in 70%-90% of patients with ANCA-associated vasculitis (AAV). Fifty percent of responders relapse within the 3-5years and currently, the mortality of AAV at 1year exceeds 15%. This article is aimed to analyze the risk-to-benefit balance of steroids and conventional immunosuppressive regimens, focusing, for a sake of brevity, on idiopathic nephrotic syndrome (INS) and ANCA associated vasculitis.