Membranous Nephropathy: Approaches to Treatment

Abstract

Background: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. This review focuses on mechanisms involved in the pathogenesis of MN and approaches to treatment of this disease. Summary: Our understanding of the pathogenesis of primary MN has advanced greatly with the identification of M-type phospholipase A₂ receptor and thrombospondin type-1 domain-containing 7A as target antigens whose antibodies serve as biomarkers of this disease. Additional research, including investigations into the roles of complement and melanocortin receptors on the podocyte, may further improve our understanding of how best to treat this condition. Immunosuppressive therapies, including corticosteroids alternating with alkylating agents, and calcineurin inhibitors are partially successful in reducing proteinuria in MN, but their use may be associated with significant adverse effects and a high relapse rate. Novel interventions, including targeting B cells with rituximab as well as treatment with adrenocorticotropic hormone (ACTH), are being investigated. Key Messages: The understanding of treatment targets and availability of new biomarkers has facilitated diagnosis and improved risk stratification for MN and may also be useful for individualizing treatment with a wider range of therapeutic options for patients with MN. Considerable evidence supports the use of B-cell depletion as initial therapy in nephrotic patients with MN. ACTH should be considered for patients who do not respond to traditional therapies such as alkylating agents and calcineurin inhibitors.

Proteinuria in Nephrotic Syndrome: Mechanistic and Clinical Considerations in Optimizing Management

“…In "Membranous Nephropathy: Approaches to Treatment," Bomback and Fervenza [3] discuss initial conservative treatment as well as approaches for those patients who are not responsive. Furthermore, they discuss the variability in clinical progression and the potential use of anti-phospholipase A 2 receptor antibodies along with proteinuria as markers for both prognosis and response to therapy, enabling a more personalized treatment approach.…”

ACTH4-10 protects the ADR-injuried podocytes by stimulating B lymphocytes to secrete IL-10

“…Firstly, the supernatants of B cells stimulated with ACTH 4-10 at three concentrations were added to the culture medium of podocytes, and then podocytes were exposed to ADR. Our current experimental treatment time of the supernatants was selected, namely 1 h, based on relevant literature [7,20,21]. Moreover, the supernatants could significantly promote the proliferation of injured podocytes compared with the ADR group.…”

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

“…Treatment with RAASi has been established in chronic proteinuric diseases. However, RAASi is not expected to have any effect in immune active disease, therefore, patients who will benefit are either at early non-nephrotic stage, or have progressed to advanced disease [17][18][19][20][21]. It is not easy to assess immunological status in PMN, although the recent finding of PLA2R-Ab can provide some information, as low levels usually represent inactive phase, predict beneficial outcome and thus, suggest treatment with RAASi and no immunosuppression [22].…”