Comparison of immunosuppressive therapeutic regimens in patients with nephrotic syndrome due to idiopathic membranous nephropathy

Abstract

In this prospective randomized trial, we compared the effects of cyclosporine-and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy. Twenty-eight patients were randomized to receive treatment with one of the three therapeutic regimens: cyclosporine with methylprednisolone, cyclophosphamide with methylprednisolone or lisinopril (control). Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period. At the end of the study period, renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group. Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group. Total cholesterol levels and proteinuria were significantly reduced in all groups. In the comparison between the groups, serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study. Six patients from the cyclosporine group (1/10 complete and 5/10 partial), all cyclophosphamide-treated (4/8 complete and 4/8 partial) and all 10 lisinopriltreated patients (10/10 partial) were on remission at the end of the study. In conclusion, cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens. Cyclophosphamide is associated with more complete remissions after 9 months of treatment. Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions.

Immunosuppression for Membranous Nephropathy

“…Sensitivity analysis confirmed that there were no significant changes when nine studies, which provided unpublished data or had a low-quality design, were excluded (12,17,28,31,36,37,39,45,46). The evidence for all-cause mortality or risk of ESRD was not consistent when prespecified subgroup analyses were undertaken (Supplemental Figures 3-5).…”

“…The reporting rates of all-cause mortality or risk of ESRD, CR or PR, proteinuria, and adverse events leading to withdrawal or hospitalization were 83% (30 of 36), 89% (32 of 36), 61% (22 of 36) and 86% (31 of 36), respectively. A total of 17 of 36 studies (47%) were classified as totally or partially unpublished or having a lowquality design (12,16,17,19,(26)(27)(28)31,(36)(37)(38)(39)(45)(46)(47)(48)(49).…”

“…Three trials were included in more than one comparison category (16,17,28) (Supplemental Table 3). The very limited effect of RAS blockers (e.g., ACEI) or corticosteroid monotherapy on the natural history of patients with IMN and nephrotic syndrome, especially for those with heavy proteinuria, has been well recognized (50,51).…”

“…Dussol et al also failed to demonstrate an effect of mycophenolate mofetil on CR + PR (15). Recent studies evaluating the effects of older immunosuppressive treatments, such as corticosteroids, alkylating agents, cyclosporine, and azathioprine, have also been published (16)(17)(18). Tripterygium wilfordii, a traditional Chinese immunosuppressive medicine, has been reported to be effective in Chinese patients (19,20).…”

“…A total of 18 trials (n=935 patients) compared no treatment/ACEI with a variety of immunosuppressive treatments, including corticosteroids, alkylating agents, cyclosporine, tacrolimus, mycophenolate mofetil, adrenocorticotropic hormone, azathioprine, and mizoribine (10,12,15,17,18,24,25,28,29,(31)(32)(33)36,37,39,42,45,46). Table 4).…”