Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2-3 mg/kg per day) in combination with low-dose methylprednisolone (4 mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. The mean duration of treatment was 11 +/- 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. The average time to achieve optimal remission was 4.2 +/- 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Pcr) did not change significantly from pre CyA levels during follow up (1.0 +/- 0.3 vs 1.2 +/- 0.3 mg/dL, P = NS). The remaining four patients who had renal insufficiency already before CyA (mean Pcr: 2.1 +/- 0.8 mg/dL), showed a rapid deterioration of renal function after the initiation of CyA(mean Pcr: 3.1 +/-1.5 mg/dL, P < 0.01), and as a consequence, the drug was discontinued. A multivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment (P < 0.02), the percentage of obsolete glomeruli (P < 0.01), and the severity of interstitial fibrosis (P < 0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.