56,57 Cattran et al. reported reduced rates of deterioration of renal function with cyclosporine in one small study of high-risk patients.56 In a study then design similar to that used by du Buf-Vereijken et al.,34,44 65 patients with IMN were initially followed conservatively for 12 months. Only patients with clear evidence of declining renal function and persistent nephrotic-range proteinuria during the observation period were randomized to receive treatment with cyclosporine for 12 months or placebo. Of 65 patients, 23 (36%) met criteria for randomization. Compared with placebo, cyclosporine-treated patients demonstrated significantly reduced proteinuria (halving of proteinuria in 50% of treated patients versus no improvement in placebo patients) and slower rates of decline in kidney function as measured by change in the slope of creatinine clearance.

These improvements were sustained in 75% of the patients for up to 2 years post-treatment. Fewer patients in the treated group progressed to end stage (11% versus 50%, respectively). In contrast, a controlled trial by the Cyclosporine in Membranous Nephropathy Study Group failed to demonstrate any long-term benefits of cyclosporine when used in patients with deteriorating renal function.58 In light of the nephrotoxic potential of calcineurin inhibitors, caution and close monitoring of blood drug levels and renal function are advised if CNIs are initiated in patients with an impaired GFR at the start of therapy and/or severe tubulointerstitial damage on renal biopsy.

No prospective randomized head-to-head comparisons of cyclosporine (or tacrolimus) to standard regimens of alkylating agents have been conducted. A retrospective study by Goumenos et al. attempted to address this issue by comparing the outcomes of patients who were treated with a 6-month Ponticelli protocol (steroids plus chlorambucil or cyclophosphamide; n=31) with those treated with cyclosporine for 2 years plus steroids (n=46).59 The use of different therapeutic regimens in the two groups reflects institutional treatment preferences over a 10-year period. Baseline characteristics of the groups were similar. More remissions occurred among the cyclosporine-treated patients than among those receiving alkylating agents (85% versus 55%; P=0.004). Relapses tended to occur more often in the cyclosporine-treated group but the differences were not significant (41% versus 29%, respectively). During a mean follow-up of 48��36 months there were no differences in rates of doubling of serum creatinine between treatment groups (26% versus 23%, respectively) or requirement for renal replacement therapy. However the design Dacomitinib and retrospective nature of the study preclude definitive comparisons of these therapies for IMN.