Treatment of Membranous Nephropathy in Patients With THSD7A Antibodies Using Immunoadsorption

Weinmann‐Menke, Julia; Holtz, Stefan; Sollinger, Daniel; Dörken, Mara; Boedecker, Simone; Schamberger, B.; Pfister, Frederick; Amann, Kerstin; Lutz, Jens

doi:10.1053/j.ajkd.2019.05.021

Cited by 19 publications

(13 citation statements)

References 8 publications

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“…Plasma exchange and immunoabsorption have been proposed in the management of pMN to rapidly decrease the titers of autoantibodies. However, only small series have been reported in patients with severe or refractory pMN ( 83 , 89 , 90 ). Plasma exchange and immunoabsorption do not directly modulate B-cell proliferation and activity, so the patients additionally received immunosuppressive treatment.…”

Section: Rituximab-refractory Membranous Nephropathymentioning

confidence: 99%

Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy

et al. 2022

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Primary membranous nephropathy (pMN) is an auto-immune disease characterized by auto-antibodies targeting podocyte antigens resulting in activation of complement and damage to the glomerular basement membrane. pMN is the most common cause of nephrotic syndrome in adults without diabetes. Despite a very heterogeneous course of the disease, the treatment of pMN has for many years been based on uniform management of all patients regardless of the severity of the disease. The identification of prognostic markers has radically changed the vision of pMN and allowed KDIGO guidelines to evolve in 2021 towards a more personalized management based on the assessment of the risk of progressive loss of kidney function. The recognition of pMN as an antibody-mediated autoimmune disease has rationalized the use immunosuppressive drugs such as rituximab. Rituximab is now a first line immunosuppressive therapy for patients with pMN with proven safety and efficacy achieving remission in 60-80% of patients. For the remaining 20-40% of patients, several mechanisms may explain rituximab resistance: (i) decreased rituximab bioavailability; (ii) immunization against rituximab; and (iii) chronic glomerular damage. The treatment of patients with rituximab-refractory pMN remains controversial and challenging. In this review, we provide an overview of recent advances in the management of pMN (according to the KDIGO 2021 guidelines), in the understanding of the pathophysiology of rituximab resistance, and in the management of rituximab-refractory pMN. We propose a treatment decision aid based on immunomonitoring to identify failures related to underdosing or immunization against rituximab to overcome treatment resistance.

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Section: Rituximab-refractory Membranous Nephropathymentioning

confidence: 99%

Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy

et al. 2022

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“…Immunoadsorption and plasmapheresis have been used by several groups to accelerate the depletion of circulating THSD7A-and PLA2R-Ab in patients with severe MN [31,32]. Only small series or cases have been reported.…”

Section: Improving the Use Of Anti-cd20 Antibodiesmentioning

confidence: 99%

Advances in Membranous Nephropathy

Ronco

Plaisier

Dębiec

2021

JCM

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Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leapcombining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

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“…In patients with PLA2R-negative and THSD7A-positive MN, IAS can also reduce proteinuria by reducing THSD7A antibody levels. However, proteinuria relapses and autoantibodies regenerate when IAS is discontinued [ 31 ]. Therefore, IAS should be an adjunctive option for severe cases.…”

Section: Ta In Primary Kidney Diseasesmentioning

confidence: 99%

Therapeutic apheresis in kidney diseases: an updated review

et al. 2022

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Besides conventional medical therapies, therapeutic apheresis has become an important adjunctive or alternative therapeutic option to immunosuppressive agents for primary or secondary kidney diseases and kidney transplantation. The available therapeutic apheresis techniques used in kidney diseases, including plasma exchange, double-filtration plasmapheresis, immunoadsorption, and low-density lipoprotein apheresis. Plasma exchange is still the leading extracorporeal therapy. Recently, growing evidence supports the potential benefits of double-filtration plasmapheresis and immunoadsorption for more specific and effective clearance of pathogenic antibodies with fewer side effects. However, more randomized controlled trials are still needed. Low-density lipoprotein apheresis is also an important supplementary therapy used in patients with recurrent focal segmental glomerulosclerosis. This review collects the latest evidence from recent studies, focuses on the specific advantages and disadvantages of these techniques, and compares the discrepancy among them to determine the optimal therapeutic regimens for certain kidney diseases.

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Treatment of Membranous Nephropathy in Patients With THSD7A Antibodies Using Immunoadsorption

Cited by 19 publications

References 8 publications

Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy

Advances in the Management of Primary Membranous Nephropathy and Rituximab-Refractory Membranous Nephropathy

Advances in Membranous Nephropathy

Therapeutic apheresis in kidney diseases: an updated review

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