The evolution of the therapeutic approach to membranous nephropathy

2020 ◽  
Author(s):  
Claudio Ponticelli ◽  
Passerini Patrizia ◽  
Lucia Del Vecchio ◽  
Francesco Locatelli
Keyword(s):  
Membranous Nephropathy ◽  
Alkylating Agent ◽  
Randomized Clinical Trials ◽  
Calcineurin Inhibitors ◽  
Phospholipase A2 Receptor ◽  
Repeated Administrations ◽  
Circulating Antibodies ◽  
Stage Renal Disease ◽  
End Stage

Abstract Primary membranous nephropathy (MN) is a frequent cause of nephrotic syndrome (NS) in adults. In untreated patients, the outcome is variable, with one-third of the patients entering remission while the remaining ones show persisting proteinuria or progression to end-stage renal disease. Randomized clinical trials reported the efficacy of a 6-month regimen alternating intravenous and oral glucocorticoids with an alkylating agent every other month. The potential side effects of this regimen were limited by the fact that the use of glucocorticoids and alkylating agent did not exceed 3 months each. Two randomized trials with follow-ups (FU) up to 10 years provided assurance about the long-term efficacy and safety of this cyclical therapy. Calcineurin inhibitors have also been used successfully. However, in most responders, NS relapsed after the drug was withdrawn. Conflicting results have been reported with mycophenolate salts and adrenocorticotropic hormone. Observational studies reported good results with rituximab (RTX). Two controlled trials demonstrated the superiority of RTX over antiproteinuric therapy alone and cyclosporine. However, the FUs were relatively short and no randomized trial has been published against cyclical therapy. The available results, together with the discovery that most patients with MN have circulating antibodies against the phospholipase A2 receptor 1, support the use of cytotoxic drugs or RTX in MN. It is difficult to choose between these two different treatments. RTX is easier to use, but the FUs of the available studies are short, thus doubts remain about the long-term risk of relapses and the safety of repeated administrations of RTX.

scholarly journals Mechanisms of Primary Membranous Nephropathy

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 513
Author(s):  
Yan Gu ◽  
Hui Xu ◽  
Damu Tang
Keyword(s):  
Membranous Nephropathy ◽  
Full Spectrum ◽  
The Past ◽  
Phospholipase A2 Receptor ◽  
Kidney Glomerulus ◽  
Recent Developments ◽  
One Step ◽  
Stage Renal Disease ◽  
End Stage ◽  
Antibody Levels

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogenous outcomes with approximately 30% of cases progressing to end-stage renal disease. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. Approximately 50–80% and 3–5% of primary MN (PMN) cases are associated with either anti-PLA2R or anti-THSD7A antibodies, respectively. The presence of these autoantibodies is used for MN diagnosis; antibody levels correlate with disease severity and possess significant biomarker values in monitoring disease progression and treatment response. Importantly, both autoantibodies are causative to MN. Additionally, evidence is emerging that NELL-1 is associated with 5–10% of PMN cases that are PLA2R- and THSD7A-negative, which moves us one step closer to mapping out the full spectrum of PMN antigens. Recent developments suggest exostosin 1 (EXT1), EXT2, NELL-1, and contactin 1 (CNTN1) are associated with MN. Genetic factors and other mechanisms are in place to regulate these factors and may contribute to MN pathogenesis. This review will discuss recent developments over the past 5 years.

scholarly journals IMMUNODIAGNOSIS IN MEMBRANOUS NEPHROPATHY

2020 ◽  
Vol 73 (9) ◽  
pp. 1861-1866
Author(s):  
Magdalena Ratajczak ◽  
Ewa Poleszak ◽  
Tomasz Chrościcki
Keyword(s):  
Membranous Nephropathy ◽  
Antinuclear Antibodies ◽  
Aim Analysis ◽  
Non Invasive ◽  
Phospholipase A2 Receptor ◽  
Secondary Form ◽  
Stage Renal Disease ◽  
End Stage ◽  
Receptor Antibodies ◽  
Primary Form

One of the diseases leading to chronic end-stage renal disease is membranous nephropathy (MN). The main cause of this disease is the formation of antibodies to foreign and native antigens. Membranous nephropathy can be conventionally divided into 2 types: primary form (when the primary disease is unknown) and secondary form. Detection of appropriate antibodies is one of the methods to recognize and differentiate primary and secondary forms. A large role in non-invasive diagnosis of MN and differentiation of the primary form from the secondary play antinuclear antibodies (ANA), antibodies against granulocyte cytoplasm (ANCA), antiglomerular basement antibodies (anti-GBM) and phospholipase A2 receptor antibodies (anti-PLA2R). Differentiation matters when choosing a treatment choice. In the primary form, it is immunosuppression, and in the form of secondary treatment, it consists in curing or controlling diseases that can cause symptoms of MN. The aim: Analysis of serological methods helpful in immunodiagnosis of membranous nephropathy.

scholarly journals Membranous nephropathy in patients with HIV: a report of 11 cases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Vivek Charu ◽  
Nicole Andeen ◽  
Vighnesh Walavalkar ◽  
Jessica Lapasia ◽  
Jin-Yon Kim ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Viral Loads ◽  
Phospholipase A2 Receptor ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Stage Renal Disease ◽  
End Stage ◽  
Nephrotic Range Proteinuria ◽  
Tissue Reactivity

Abstract Background Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied. Methods We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded. Results We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4–145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period. Conclusions MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.

Membranous nephropathy

2020 ◽  
pp. 4928-4933
Author(s):  
An S. De Vriese ◽  
Fernando C. Fervenza
Keyword(s):  
High Risk ◽  
Membranous Nephropathy ◽  
Alkylating Agents ◽  
Calcineurin Inhibitors ◽  
Treatment Regimens ◽  
Phospholipase A2 Receptor ◽  
Risk Of Progression ◽  
Long Term Prognosis ◽  
Asymptomatic Proteinuria

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in Caucasians adults. It may also present with asymptomatic proteinuria. Its defining feature is the presence of subepithelial immune deposits, localized between the podocyte and the glomerular basement membrane. Aetiology—primary MN (80% of cases) is caused in most cases by antibodies against the M-type phospholipase A2 receptor (PLA2R). Secondary MN occurs as a consequence of drugs, malignancy, or autoimmune disease. Prognosis—the clinical course of primary MN is variable: spontaneous complete remission of proteinuria occurs in 20 to 30% and progressive kidney failure develops in 20 to 40% over 5 to 15 years. Patients with gross proteinuria (>8 g/day) are at high risk of progression, as are those with a high and rising anti-PLA2R antibody level. Management—patients at low risk of progression have an excellent long-term prognosis and should be treated conservatively without immunosuppression. Patients at medium and high risk for progression benefit from immunosuppression in addition to conservative treatment. Corticosteroid monotherapy is ineffective in primary MN and should not be used. Standard treatment regimens include corticosteroids with alkylating agents (chlorambucil, cyclophosphamide), corticosteroids with mycophenolate mofetil, and calcineurin inhibitors (ciclosporin, tacrolimus). Early experience with rituximab has given some promising results.

Primary membranous nephropathy: comprehensive review and historical perspective

2019 ◽  
Vol 95 (1119) ◽  
pp. 23-31 ◽  
Author(s):  
Krishna C Keri ◽  
Samuel Blumenthal ◽  
Varsha Kulkarni ◽  
Laurence Beck ◽  
Tepsiri Chongkrairatanakul
Keyword(s):  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Adrenocorticotropic Hormone ◽  
Disease Process ◽  
Serologic Marker ◽  
Phospholipase A2 Receptor ◽  
Stage Renal Disease ◽  
End Stage ◽  
Over 40 Years

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age. It has an estimated incidence of 8–10 cases per 1 million. Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years. Although it was recognised as a distinct clinic-pathological entity in 1940s by immunofluorescence and electron microscopy, the pathogenesis and treatment have become more apparent only in the last decade. Discovery of M-type phospholipase A2 receptor (PLA2R) antibodies and thrombospondin type 1 domain-containing 7A antibodies has given new perspectives in understanding the pathogenesis of the disease process. Anti-PLA2R antibody is the first serologic marker that has promising evidence to be used as a tool to prognosticate the course of the disease. More importantly, therapeutic agents such as rituximab and adrenocorticotropic hormone analogues are the newer therapeutic options that should be considered in the therapy of primary MN.

Frequency of Gastrointestinal Diseases in Patients with End-Stage Renal Disease Treated with Long Term Dialysis

2018 ◽  
Vol 2 (2) ◽  
pp. 105-112
Author(s):  
Lutfi Zylbeari ◽  
Zamira Bexheti ◽  
Gazmend Zylbeari ◽  
Ferizate Haxhirexha ◽  
Kastriot Haxhirexha
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Gastrointestinal Diseases ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups

2021 ◽  
Author(s):  
Geir Mjøen ◽  
Umberto Maggiore ◽  
Nicos Kessaris ◽  
Diederik Kimenai ◽  
Bruno Watschinger ◽  
...  
Keyword(s):  
Evaluation Process ◽  
Kidney Donation ◽  
Kidney Donors ◽  
Living Kidney Donors ◽  
Relative Risks ◽  
Written Information ◽  
The Difference ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. Methods All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. Results The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. Conclusions The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.

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