How to Choose the Right Treatment for Membranous Nephropathy

Abstract

Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.

Keywords: belimumab; bortezomib; complement children; glomerulonephritis; immunosuppressive therapy; membranous nephropathy; nephrotic syndrome; pregnancy; renal transplant; rituximab.

Figure 1

History of discovery of various antigens. FAT1, protocadherin FAT1; HTRA1, serine protease HTRA1; MN, membranous nephropathy; NCAM1, neural cell adhesion molecule 1; NEP, neutral endopeptidase; NELL, neural-tissue-encoding protein with EGF-like repeats; NTNG1, netrin G1; PCDH7, protocadherin 7; PLA2R, phospholipase A2 receptor 1; pMN, primary membranous nephropathy; TGFBR3, transforming growth factor beta receptor 3; TSHD7A, thrombospondin.

Figure 2

Different therapeutic options for the symptomatic treatment of MN. ACEi, angiotensin-converting enzyme (ACE) inhibitors; ARB, angiotensin-receptor blockers.

Figure 3

Schematic representation of different subgroups with different risk levels of progression toward end-stage renal disease. eGFR, estimated glomerular filtration rate.

Figure 4

Schematic representation of different subgroups with respective therapy. CYC, cyclophosphamide; CNI, calcineurin inhibitors; RTX, rituximab.