Treatment of severe nephrotic syndrome

Treatment modalities in severe nephrotic syndrome have to consider (a) the underlying glomerular diseases as well as (b) the extrarenal complications. Occasionally acute renal failure develops on the basis of an unknown nephrotic syndrome; if a primary glomerular disease is diagnosed by biopsy, immunosuppressive therapy is optional. In type I and type II diabetes development of a severe nephrotic syndrome is usually not reversible. To avoid the rapid decline of renal function a consequent antihypertensive therapy is the treatment of choice in this stage of the disease. Treatment of primary glomerular diseases with severe (NS) includes frequently relapsing minimal change nephropathy (MCN) that can be treated with prednisolone 1 mg/kg/day until remission occurs. For prolongation of the remission cyclophosphamide 2 mg/kg/day for eight weeks, or alternatively cyclosporine A 3 to 5 mg/kg/day for six months, can be given. In steroid-resistant focal segmental glomerulosclerosis (FSGS) eight weeks of treatment with cyclophosphamide 2.5 mg/kg/day or six months treatment with cyclosporine A 3 to 5 mg/kg/day can induce a partial or complete remission in up to 20% of the patients. In membranous glomerulopathy with severe NS, one month of therapy with prednisolone followed by chlorambucil for one month (all together 6 months) improves the renal outcome of the patients compared to controls. Alternatively, cyclophosphamide 2 mg/kg/day plus 30 mg prednisolone/day can be given for a couple of months. Extrarenal complications of a severe NS are: (a) edema; (b) thromboembolism; and (c) lipid abnormalities. If nephrotic patients are resistant to orally administered loop diuretics, they should be treated in addition intravenously with hydrochlorothiazide p.o. Nephrotic patients with a serum albumin level < 20 g/liter should be routinely anticoagulated. Extensive hyperlipidemia in severe NS can be treated with HMG-CoA reductase inhibitors.