Treatment of the nephrotic syndrome with cyclosporin A

Abstract

The three main causes of primary nephrotic syndrome are minimal change nephropathy, focal glomerulosclerosis and membranous nephropathy. Corticosteroids obtain remission of proteinuria in most patients with minimal change nephropathy. Many patients, however, show either frequent relapses or steroid dependency. A short course of cyclophosphamide or chlorambucil can achieve stable remission in many of these patients but alkylating agents cannot be repeated, their toxicity being cumulative. Analyses of the available studies showed that some 80% of patients can be maintained in remission with cyclosporin A (CsA) but relapse occurs when the drug is stopped. Severe side effects are rare. In particular, the mean values of creatinine clearance did not deteriorate in cyclosporin-treated patients and repeat renal biopsy showed only mild changes in some patients. There is no definite treatment for focal glomerulosclerosis. An analysis of 10 clinical trials showed that some 17% of nephrotic patients may enter complete remission of proteinuria and another 13% may attain partial remission of the nephrotic syndrome with CsA. There is concern over the use of this drug since cases of irreversible renal dysfunction have been reported. However, retrospective reviews of the available studies showed that the mean serum creatinine levels did not modify if patients had normal renal function when given CsA. A 6-month course of methylprednisolone and chlorambucil may obtain remission of the nephrotic syndrome in some 60% of patients with membranous nephropathy. Some trials have shown that CsA may improve proteinuria and there is also some suggestion that the drug might protect against renal function deterioration. Thus, when given at correct doses, CsA may exert an anti-proteinuric effect without deteriorating renal function, suggesting that the drug may represent a further tool in treating the primary nephrotic syndrome.