Our experience in the treatment of membranous nephropathy with cyclosporine

In a group of 17 patients with primary membranous glomerulonephritis, we assessed the impact of cyclosporine therapy on proteinuria and glomerular filtration. The indications for treatment with cyclosporine were: nephrotic syndrome resistant to chlorambucil (10 patients), cyclophosphamide (2 patients) or cyclophosphamide and chlorambucil (1 patient). We also treated with cyclosporine 3 patients with a high risk of thromboembolic complications (proteinuria above 10 g/24 hours) and one young patient was treated with cyclosporine at a dose not exceeding the gonadotoxic dose of cyclophosphamide. Treatment was started at a dose of 5 mg/kg/day and adjustments in dosages were made to achieve a trough plasma level of cyclosporine between 80-120 ng/ml, as measured by High Performance Liquid Chromatography. Simultaneously, we administered corticosteroids in a daily dose of 20 mg of prednisone or less. We followed the levels of proteinuria, serum creatinine and creatinine clearance before the treatment with cyclosporine, after one year of treatment, and at one and two years after withdrawal of cyclosporine. After one year of therapy, we observed a decline in proteinuria from 10.5 (3.1-35) to 1.7 (0.22-17.4) g/24 hours [median (range)]. This was a statistically significant decline remaining one and two years after stopping cyclosporine (Wilcoxon's paired test p < 0.01). The decline in proteinuria, after either one year of treatment and at one year after stopping treatment, was also significant in the subset of patients with membranous nephropathy refractory to chlorambucil. Our evaluation of changes in glomerular filtration using the reciprocal value of serum creatinine revealed a possible transient decline in renal function after one year of cyclosporine therapy, but we did not observe a corresponding change in creatinine clearance. Our experience confirms the importance of cyclosporine in the treatment of membranous nephropathy and shows the effectiveness of this drug even in cases refractory to prior treatment with chlorambucil.

Keywords: cyclosporine; membranous nephropathy; glomerulonephritis