scholarly journals Perspectives in membranous nephropathy

2021 ◽  
Author(s):  
Nicola M. Tomas ◽  
Tobias B. Huber ◽  
Elion Hoxha
Keyword(s):  
Membranous Nephropathy ◽  
Treatment Strategies ◽  
Diagnosis And Treatment ◽  
Clinical Use ◽  
Podocyte Injury ◽  
Open Questions ◽  
Phospholipase A2 Receptor ◽  
Future Treatments ◽  
Made In

AbstractThe identification of the phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) as podocyte antigens in adult patients with membranous nephropathy (MN) has strongly impacted both experimental and clinical research on this disease. Evidence has been furnished that podocyte-directed autoantibodies can cause MN, and novel PLA2R- and THSD7A-specific animal models have been developed. Today, measurement of serum autoantibody levels and staining of kidney biopsies for the target antigens guides MN diagnosis and treatment worldwide. Additionally, anti-PLA2R antibodies have been proven to be valuable prognostic biomarkers in MN. Despite these impressive advances, a variety of questions regarding the disease pathomechanisms, clinical use of antibody measurement, and future treatments remain unanswered. In this review, we will outline recent advances made in the field of MN and discuss open questions and perspectives with a focus on novel antigen identification, mechanisms of podocyte injury, clinical use of antibody measurement to guide diagnosis and treatment, and the potential of innovative, pathogenesis-based treatment strategies.

Diagnosis and Treatment of MODY: An Updated Mini Review

2021 ◽  
Vol 11 (20) ◽  
pp. 9436
Author(s):  
Abegail Tshivhase ◽  
Tandi Matsha ◽  
Shanel Raghubeer
Keyword(s):  
Type 2 Diabetes ◽  
Single Gene ◽  
Treatment Strategies ◽  
Diagnosis And Treatment ◽  
Endogenous Insulin ◽  
Appropriate Treatment ◽  
Mild Hyperglycemia ◽  
Onset Of Diabetes

Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset of diabetes (<25 years), insulin resistance, and preservation of endogenous insulin secretion. Currently, 14 MODY subtypes have been identified, with differences in incidence, clinical features, diabetes severity and related complications, and treatment response. This type of diabetes is mostly misdiagnosed as either type 1 or type 2 diabetes mellitus because it is difficult to differentiate between these forms of diabetes due to clinical similarities, the high cost of genetic testing, and lack of awareness. As a result, thousands of patients are not receiving appropriate treatment. Accurate diagnosis would allow for more effective therapeutic management and treatment strategies that are distinct from those used for type 1 and type 2 diabetes. This review serves to explore MODY subtypes, diagnosis, and treatment, and increase awareness of MODY incidence.

Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese Patients

2021 ◽  
pp. CJN.11860720
Author(s):  
Guoqin Wang ◽  
Lijun Sun ◽  
Hongrui Dong ◽  
Yanyan Wang ◽  
Xiaoyi Xu ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Characteristics ◽  
Chinese Patients ◽  
Double Positive ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
Pathologic Features ◽  
Glomerular Deposits ◽  
Epidermal Growth

Background and objectivesThe neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1–positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear.Design, setting, participants, & measurementsA total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened. Glomerular immunohistochemistry staining for NELL-1 was performed in 43 patients with PLA2R- and THSD7A-negative membranous nephropathy, 31 patients with PLA2R-positive membranous nephropathy, and two patients with PLA2R and THSD7A double positivity. The NELL-1 antibody was also detected in the sera of patients with NELL-1–positive membranous nephropathy by western blot. Clinical and pathologic features were comparable between patients with isolated NELL-1–positive, isolated PLA2R/THSD7A-positive, and triple antigen–negative membranous nephropathy.ResultsAmong the 832 patients with primary membranous nephropathy, 11 of 54 (20%) patients with PLA2R-negative membranous nephropathy had THSD7A-positive membranous nephropathy. NELL-1–positive membranous nephropathy accounted for 35% (15 of 43) of all patients with PLA2R- and THSD7A-negative membranous nephropathy. One patient was double positive for NELL-1 and PLA2R in glomerular deposits and positive for only the PLA2R antibody in the serum. Most patients with NELL-1–positive membranous nephropathy were women. No tumors were found. There were significant differences in the prevalence of IgG subtypes between patients with different antigen positivity. Among patients with isolated NELL-1–positive membranous nephropathy, although 80% (12 of 15) were IgG4 staining positive, the proportion of IgG4 dominance was only 67% (ten of 15).ConclusionsAbout one third of patients who were PLA2R and THSD7A negative were NELL-1 positive in Chinese patients with primary membranous nephropathy. NELL-1–positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.

A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients

2020 ◽  
Vol 97 (5) ◽  
pp. 913-919 ◽  
Author(s):  
Catherine Meyer-Schwesinger ◽  
Nicola M. Tomas ◽  
Silke Dehde ◽  
Larissa Seifert ◽  
Irm Hermans-Borgmeyer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor

Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain

2018 ◽  
Vol 31 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Vincenzo L’Imperio ◽  
Federico Pieruzzi ◽  
Renato Alberto Sinico ◽  
Manuela Nebuloni ◽  
Antonio Granata ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Immunohistochemical Staining ◽  
Phospholipase A2 Receptor ◽  
In Situ Detection

scholarly journals Development and validation of a discrimination model between primary PLA2R-negative membranous nephropathy and minimal change disease confirmed by renal biopsy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Wu ◽  
Yiding Zhang ◽  
Wen Cui ◽  
Yijun Dong ◽  
Yingyang Geng ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Minimal Change Disease ◽  
Treatment Strategies ◽  
Test Group ◽  
Minimal Change ◽  
Specific Marker ◽  
Discrimination Ability ◽  
Discrimination Model ◽  
Phospholipase A2 Receptor

AbstractMembranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical features but different treatment strategies and prognoses. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. A total 949 patients who were pathologically diagnosed as idiopathic MN or MCD were enrolled in this study, including 805 idiopathic MN and 144 MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop a discrimination model. A novel model including age, albumin, urea, high density lipoprotein, C3 levels and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has great differential capability (with an AUC of 0.904 in training group and an AUC of 0.886 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.

scholarly journals Membranous nephropathy associated with viral infection

2020 ◽  
Author(s):  
Aikaterini Nikolopoulou ◽  
Catarina Teixeira ◽  
H Terry Cook ◽  
Candice Roufosse ◽  
Thomas H D Cairns ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Viral Infection ◽  
Membranous Nephropathy ◽  
Spontaneous Remission ◽  
Outcome Data ◽  
Phospholipase A2 Receptor ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hepatitis Infection

Abstract Background Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear. Methods We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies. Results The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23–74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22–2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65–1898); P = 0.18 Mann–Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis. Conclusions We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

scholarly journals Exostosin 1/Exostosin 2–Associated Membranous Nephropathy

2019 ◽  
Vol 30 (6) ◽  
pp. 1123-1136 ◽  
Author(s):  
Sanjeev Sethi ◽  
Benjamin J. Madden ◽  
Hanna Debiec ◽  
M. Cristine Charlesworth ◽  
LouAnn Gross ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Validation Cohort ◽  
Laser Microdissection ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
And Control

BackgroundIn membranous nephropathy (MN), which is characterized by deposition of immune complexes along the glomerular basement membrane (GBM), phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain–containing 7A are target antigens in approximately 70% and 1%–5% of cases of primary MN, respectively. In other cases of primary MN and in secondary MN, the target antigens are unknown.MethodsWe studied 224 cases of biopsy-proven PLA2R-negative MN and 102 controls (including 47 cases of PLA2R-associated MN) in pilot and discovery cohorts. We also evaluated 48 cases of PLA2R-negative presumed primary MN and lupus MN in a validation cohort. We used laser microdissection and mass spectrometry to identify new antigens, which were localized by immunohistochemistry.ResultsMass spectrometry detected exostosin 1 (EXT1) and exostosin 2 (EXT2) in 21 cases of PLA2R-negative MN, but not in PLA2R-associated MN and control cases. Immunohistochemistry staining revealed bright granular GBM staining for EXT1 and EXT2. Clinical and biopsy findings showed features of autoimmune disease, including lupus, in 80.7% of the 26 EXT1/EXT2-associated MN cases we identified. In the validation cohort, we confirmed that EXT1/EXT2 staining was detected in pure class 5 lupus nephritis (eight of 18 patients) and in presumed primary MN associated with signs of autoimmunity (three of 16 patients); only one of the 14 cases of mixed class 5 and 3/4 lupus nephritis was positive for EXT1/EXT2. Tests in seven patients with EXT1/EXT2-associated MN found no circulating anti-exostosin antibodies.ConclusionsA subset of MN is associated with accumulation of EXT1 and EXT2 in the GBM. Autoimmune disease is common in this group of patients.

scholarly journals Wenyang Lishui Decoction Ameliorates Podocyte Injury in Membranous Nephropathy Rat and Cell Models by Regulating p53 and Bcl-2

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Lu ◽  
Yuezhong Luo ◽  
Baolin Su ◽  
Shuifu Tang ◽  
Gangyi Chen ◽  
...  
Keyword(s):  
Kidney Function ◽  
Aqueous Extract ◽  
Membranous Nephropathy ◽  
Molecular Mechanisms ◽  
Distilled Water ◽  
Cell Models ◽  
Clinical Trial Registry ◽  
Podocyte Injury ◽  
Phospholipase A2 Receptor ◽  
Significant Difference

Wenyang Lishui decoction (WYD) has been frequently used to treat patients with membranous nephropathy (MN) in China. Our previous study in vitro showed that WYD aqueous extract could alleviate F-actin reorganization of podocytes induced by serum from idiopathic membranous nephropathy (IMN) patients. This study aims to investigate the effects and molecular mechanisms of WYD on MN. MN rat models were induced by cationic bovine serum albumin. Experimental rats were divided into four groups: normal, model, WYD, and benazepril. The normal group consisted of normal rats receiving distilled water for four weeks, while the model, WYD, and benazepril groups consisted of MN rats receiving distilled water, 16.5 g/kg/day WYD aqueous extract, and 10 mg/kg/day benazepril, respectively. Alanine aminotransferase, kidney function, albumin, and 24 h urine total protein (UTP) were measured. Hematoxylin-eosin and electron microscopy analyses were performed. Mouse podocytes were induced to develop cell models by serum from IMN patients with antibody to the M-type phospholipase A2 receptor and spleen and kidney Yang deficiency syndrome. They were divided into five groups: control, model, 2 mg/ml WYD, 4 mg/ml WYD, and 8 mg/ml WYD. CCK-8 assays, flow cytometry, qRT-PCR, and Western blot analyses were performed. In the animal experiment, side effects of WYD were not found. Also, there was no significant difference in kidney function among the groups. In addition, UTP level was significantly reduced, and kidney histological damage was restored in both WYD and benazepril groups but difference in UTP level between them was not found. In the cell experiment, apoptosis rate was increased in the model group while it was decreased by coincubation with WYD. Besides, mRNA and protein levels of p53 were decreased, and those of Bcl-2 were increased by treatment using WYD. In conclusion, WYD could reduce proteinuria and ameliorate podocyte injury by regulating the expression of p53 and Bcl-2. The study is registered in the Chinese Clinical Trial Registry (ChiCTR-OCH-14005137).

scholarly journals Clinicopathological features in membranous nephropathy with cancer: A retrospective single-center study and literature review

2019 ◽  
Vol 34 (4) ◽  
pp. 406-413
Author(s):  
Dan Zhang ◽  
Chong Zhang ◽  
Fan Bian ◽  
Wenzhu Zhang ◽  
Gengru Jiang ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinicopathological Characteristics ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Patients With Cancer ◽  
Phospholipase A2 Receptor ◽  
Single Center Study ◽  
Close Relationship ◽  
Circulating Antibodies

Background: Membranous nephropathy is the most common glomerular disease related to malignancy. However, it is difficult to distinguish between true malignancy-related membranous nephropathy and idiopathic membranous nephropathy coincident with cancer. It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy. Therefore, the aim of this study was to compare the clinicopathological characteristics between membranous nephropathy patients with cancer and idiopathic membranous nephropathy patients without cancer to better detect malignancy-related membranous nephropathy, including glomerular PLA2R and THSD7A depositions and their circulating antibodies, together with glomerular IgG4 deposition. Methods: Twelve membranous nephropathy patients with cancer and 257 idiopathic membranous nephropathy patients without cancer were included in this study and had been followed up for more than 1 year. The glomerular expression of PLA2R, THSD7A, and IgG4 was analyzed by immunohistochemistry. Circulating anti-PLA2R and anti-THSD7A antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence testing, respectively. Results: Membranous nephropathy patients with cancer were significantly older and had higher serum creatinine and a lower estimated glomerular filtration rate than idiopathic membranous nephropathy patients ( P<0.05). The positive rates of glomerular PLA2R and IgG4 depositions and circulating anti-PLA2R antibodies in membranous nephropathy patients with cancer were significantly lower than those in idiopathic membranous nephropathy patients without cancer ( P<0.01). Conclusion: The absence of glomerular PLA2R deposition and negative circulating anti-PLA2R antibodies, along with negative glomerular IgG4 staining, may be useful clues to more accurately screen underlying malignancies in membranous nephropathy patients.

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