Introduction
The use of cyclophosphamide with corticosteroids for the management of membranous nephropathy (MN) is associated with significant safety concerns. Several retrospective studies suggest that a lower dose may effectively induce remission in MN participants. This randomized trial assessed whether the lower dose of cyclical cyclophosphamide/corticosteroids was non-inferior to the standard-dose in patients with MN.
Methods
We randomly assigned 114 participants (32 women and 82 men) to receive either the low-dose (prednisolone-0.50 mg/kg/day during months-1,3, and 5, along with oral CYC-1.0-1.5 mg/kg/day during months-2,4 and 6) or the standard-dose cyclophosphamide/corticosteroids (Methylprednisolone-1 g/day for 3 days, followed by prednisolone-0.50 mg/kg/day during months-1,3, and 5, along with oral CYC-2.0-2.5 mg/kg/day during months-2,4 and 6). The primary outcome- complete (CR) or partial remission (PR) of proteinuria between months 6 and 24.
Results
A total of 57 participants were randomized into each group. The mean age was 41.53±12.29 years, median proteinuria, mean serum albumin, and creatinine levels were 6.83 g/day (IQR 5.02-10.15), 2.34±0.59 g/dl and 0.92±0.33 mg/dl were comparable between groups. In the intention-to-treat analysis, 45 participants (78.94%) in the low-dose group and 50 participants (87.71%) in the standard-dose group achieved the primary outcome (treatment difference-8.78 %, confidence interval(CI), -0.24 to 0.067), and met the criteria for non-inferiority (p=0.009). Forty-five (78.94%) and 55 (96.49%) participants receiving the low-dose and standard-dose cyclophosphamide/corticosteroids experienced at least one adverse event (difference -17.54 % CI- 1.52% to 33.45%).
Conclusion
The results suggest that low-dose cyclophosphamide/corticosteroids may be as effective as the standard-dose of cyclical cyclophosphamide/corticosteroids in achieving proteinuria remission in MN.