Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy

Abstract

Immunosuppressive therapy is mandatory for primary membranous nephropathy with persistent nephrotic proteinuria or anti-phospholipase A2 receptor antibodies, reduced kidney function, or another risk factor for progression. Rituximab has demonstrated efficacy for proteinuria remission compared with renin-angiotensin system blockade or cyclosporine in two well-powered randomized controlled trials. More recently, STARMEN showed that alternating glucocorticoid-cyclophosphamide is superior to sequential tacrolimus-rituximab for proteinuria remission, although it was associated with a higher risk of non-serious adverse events. However, sequential tacrolimus-rituximab involved delayed lower dose rituximab and was the worst-performing rituximab regimen among those tested in randomized clinical trials. The RI-CYCLO pilot study did not demonstrate superiority of glucocorticoid-cyclophosphamide over rituximab and found no difference in adverse events. Overall, STARMEN and RI-CYCLO confirmed the efficacy of glucocorticoid-cyclophosphamide in patients with high-risk membranous nephropathy and the role of rituximab as a valid alternative. However, none of the trials tested an optimized rituximab protocol involving a second rituximab cycle before declaring treatment failure. Calcineurin inhibitors should be considered third-line drugs and sequential use of calcineurin inhibitor rituximab did not add over rituximab-only regimens. We critically review recent randomized controlled trials, propose a research agenda, and call for multinational pragmatic trials that enroll patients at referral centers to address unmet research needs.

The Efficacy of Cyclophosphamide Combined with Prednisone in Membranous Nephropathy Patients with Different Cytochrome P450 2B6 Gene Polymorphisms and Analysis of Factors Influencing the Efficacy

“…), glucocorticoids and immunosuppressive therapy. 13 Glucocorticoids can affect human glucose metabolism, and the glucocorticoids commonly used in clinical treatment are prednisone and hydrocortisone. Among which, prednisone can reduce cell membrane and capillary permeability, reduce the inflammatory response, inhibit the release of histamine, promote the decomposition of immune complexes, and reduce the utilization of glucose, thus reducing the inflammatory response and reducing the accumulation of immune complexes.…”

Profile and primary treatment outcomes in membranous nephropathy

“…A total of 50 patients were treated with rituximab as initial line of therapy. They were administered 4 weekly doses of 375 mg/m 2 rituximab intravenously or 1000 mg of rituximab on day one and 15 in the last 4 patients. A single booster dose of 375 mg/m 2 rituximab was administered at 6 months in 4 patients.…”

“…Various treatment regimens have been used for IMN including methylprednisolone, cyclosporine, chlorambucil, cyclophosphamide, tacrolimus, and recently rituximab. 2 It has been seen that corticosteroids and alkylating agents used in combination were helpful in maintaining and preserving long term kidney function. Recently, rituximab has been a major player as it avoids long term nephrotoxicity associated with alkylating agents and calcineurine inhibitors and also avoids the high risk of relapse seen with them.…”

“… 1 It is the leading cause of nephrotic syndrome in adults. 2 Most of adults (80%) with idiopathic membranous nephropathy (IMN) present with nephrotic syndrome and the rest present with sub nephrotic proteinuria. Spontaneous remissions and relapses are seen in the disease course.…”

“…Various treatment regimens have been used for IMN including methylprednisolone, cyclosporine, chlorambucil, cyclophosphamide, tacrolimus, and recently rituximab. 2 …”