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K Dahan
Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature...
May 25, 2016: La Revue de Médecine Interne
Edward J Filippone, John L Farber
Membranous nephropathy (MN) may occur in a kidney transplant as recurrence of the original disease (rMN) or as a de novo MN (dnMN). rMN often occurs early, within the first year, and often in a mild or subclinical fashion. Recurrence cannot be predicted by clinical features at the time of transplantation. The natural history is increasing proteinuria over time, with less chance for spontaneous remission compared to primary MN (pMN). Antiphospholipase A2 receptor (PLA2R) antibodies should be evaluated in all patients with pMN at the time of transplantation and serially...
September 20, 2016: Clinical Transplantation
Li Lin, Wei Ming Wang, Xiao Xia Pan, Jing Xu, Chen Ni Gao, Wen Zhang, Hong Ren, Jing Yuan Xie, Pin Yan Shen, Yao Wen Xu, Li Yan Ni, Nan Chen
Anti-M-type phospholipase A2 receptor (anti-PLA2R) is a widely accepted biomarker for clinical idiopathic membranous neurophathy (IMN). However, its ability to differentiate between IMN and secondary MN (SMN) is controversial. The objective of this study was to assess clinical MN biomarkers in blood, tissue and urine samples from Chinese patients. In total, 195 MN patients and 70 patients with other glomerular diseases were prospectively enrolled in the study. Participants were followed up for average of 17 months (range 3-39 months)...
September 13, 2016: Oncotarget
Jiqiu Wen, Kenan Xie, Mingchao Zhang, Jinsong Chen, Jiong Zhang, Dongrui Cheng, Xue Li, Shuming Ji, Zhihong Liu
Idiopathic membranous nephropathy (IMN) is known to be associated with antibodies acting on the M-type phospholipase A2 receptor (PLA2R) of the podocyte. However, the mechanism underlying de novo membranous nephropathy (dn MN) posttransplantation remains unclear. In this study, we aimed to elucidate the mechanism underlying dn MN.We selected 8 cases with dn MN and compared them to 20 IMN cases. Fifteen cases of stable grafts were selected as controls.Several differences between the dn MN group and the IMN group were detected...
September 2016: Medicine (Baltimore)
Ruimin Hu, Guolan Xing, Huijuan Wu, Zhigang Zhang
BACKGROUND: The concomitant presence of idiopathic membranous nephropathy and IgA nephropathy is rare. Here, we report 9 cases of phospholipase-A2-receptor (PLA2R) positive idiopathic membranous nephritis combined with IgA nephropathy, while reviewing publications regarding the pathological characteristics of this glomerolonephritis complication. CASE PRESENTATION: Nine cases of renal biopsy tissues were retrospectively reviewed, including the clinicopathological features, the results of the immunofluorescence assays, and the electron microscopic examination...
2016: Diagnostic Pathology
Talal Alfaadhel, Daniel Cattran
BACKGROUND: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome (NS) in adults in Western countries. In 2012, the KDIGO (Kidney Disease: Improving Global Outcomes) working group published guidelines for the management of glomerulonephritis, thus providing a template for the treatment of this condition. While being aware of the impact of the clinicians' acumen and that patients may choose a different therapeutic option due to the risks of specific drugs and also of the evolving guidelines, this review details our approach to the management of patients with IMN in a Western center (Toronto)...
September 2015: Kidney Diseases
Jing Xu, Xiaofan Hu, Jingyuan Xie, Nan Chen
BACKGROUND: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in adults, accounting for about 20.0% of all NS cases. With an increasing prevalence, especially in the elderly, it has received great attention in Asia. SUMMARY: Recently, the prevalence of idiopathic MN (IMN) has significantly increased among the elderly people in Asia and other places in the world. Although the exact mechanism of IMN remains unveiled, the identification of new antigens such as PLA2R and THSD7A has greatly enhanced our understanding of its pathogenesis...
September 2015: Kidney Diseases
Anne-Els van de Logt, Julia M Hofstra, Jack F Wetzels
INTRODUCTION: Therapy in patients with primary membranous nephropathy is debated. The discovery of anti-PLA2R antibodies provides opportunities for new treatment strategies. AREAS COVERED: The PubMed database and Cochrane library were searched for full-text articles published in English before March 2016. The search terms included 'Glomerulonephritis, Membranous' [MESH], 'membranous glomerulonephritis' [tiab] and, 'idiopathic membranous nephropathy' [tiab] and 'membranous nephropathy' [tiab], in combination with 'Therapeutics' [MESH], 'therapeutic*'[tiab], 'immunosuppression' [MESH] and 'immunosuppression' [tiab]...
September 16, 2016: Expert Review of Clinical Pharmacology
N Gopalakrishnan, P Abeesh, T Dineshkumar, S Murugananth, R Sakthirajan, G Srinivasa Raman, J Dhanapriya, T Balasubramaniyan, Md Haris
We conducted a prospective study to assess utility of detection of antibodies to phospholipase A2receptor (PLA2R) in the serum of patients with membranous nephropathy. Seventy five patients with biopsy proven membranous nephropathy admitted between January 2011 and September 2014 were studied. Serum anti- PLA2R was tested by indirect immunofluorescence. The test was positive in 45 out of 60 patients with primary membranous nephropathy (PMN) and in none of the 15 patients with secondary membranous nephropathy, with a sensitivity of 75% and specificity of 100% for PMN...
July 2016: Indian Journal of Nephrology
Keiichi Kubota, Junichi Hoshino, Toshiharu Ueno, Koki Mise, Ryo Hazue, Akinari Sekine, Junko Yabuuchi, Masayuki Yamanouchi, Tatsuya Suwabe, Koichi Kikuchi, Keiichi Sumida, Noriko Hayami, Naoki Sawa, Kenmei Takaichi, Takeshi Fujii, Kenichi Ohashi, Shinichi Akiyama, Shoichi Maruyama, Yoshifumi Ubara
A 95-year-old woman was admitted to our hospital for evaluation of bilateral lower-limb edema persisting for 3 months. Serum creatinine was 1.55 mg/dl, and urinary protein excretion was 9.1 g/day. Renal biopsy revealed stage 1 membranous glomerulonephritis (MGN) with immunoglobulin G4-dominant staining. This patient did not have any underlying disease such as infection with hepatitis B or C virus or malignancy, and anti-phospholipase A2 receptor (PLA2R) antibody was detected in the serum. Accordingly, idiopathic MGN was diagnosed...
May 2016: Case Reports in Nephrology and Dialysis
Gabriella Moroni, Federica Depetri, Lucia Del Vecchio, Beniamina Gallelli, Francesca Raffiotta, Elisa Giglio, Francesca Brunini, Marco D'Amico, Selena Longhi, Antonella Radice, Piergiorgio Messa, Renato Alberto Sinico
BACKGROUND: The optimal dosing and the efficacy of rituximab for primary membranous nephropathy (PMN) has not been established. This multicentric prospective study evaluates the efficacy and safety of low-dose rituximab (RTX) therapy in patients with PMN in clinical practice. METHODS: Thirty-four consecutive patients with PMN and nephrotic syndrome were included and received RTX (375 mg/m(2)) once (18 patients) or twice (16 patients). RTX was the first-line therapy for 19 (56%) and the second line for 15 (44%) patients...
July 6, 2016: Nephrology, Dialysis, Transplantation
Kei Hihara, Masayuki Iyoda, Shohei Tachibana, Ken Iseri, Tomohiro Saito, Yasutaka Yamamoto, Taihei Suzuki, Yukihiro Wada, Kei Matsumoto, Takanori Shibata
The phospholipase A2 receptor (PLA2R) is the major target antigen (Ag) in idiopathic membranous nephropathy (IMN). Recently, several types of immunoassay systems for anti-PLA2R antibody (Ab) have been developed. However, the correlation of serum anti-PLA2R Abs and glomerular expression of PLA2R Ag, and their association with clinicopathological characteristics have yet to be proven in Japanese patients. We examined serum anti-PLA2R Abs by both ELISA and cell-based indirect immunofluorescence assay (CIIFA), and glomerular PLA2R expression by immunofluorescence (IF) in 59 biopsy-proven MN patients including IMN (n = 38) and secondary MN (SMN) (n = 21)...
2016: PloS One
Karine Dahan, Hanna Debiec, Emmanuelle Plaisier, Marine Cachanado, Alexandra Rousseau, Laura Wakselman, Pierre-Antoine Michel, Fabrice Mihout, Bertrand Dussol, Marie Matignon, Christiane Mousson, Tabassome Simon, Pierre Ronco
Randomized trials of rituximab in primary membranous nephropathy (PMN) have not been conducted. We undertook a multicenter, randomized, controlled trial at 31 French hospitals (NCT01508468). Patients with biopsy-proven PMN and nephrotic syndrome after 6 months of nonimmunosuppressive antiproteinuric treatment (NIAT) were randomly assigned to 6-month therapy with NIAT and 375 mg/m(2) intravenous rituximab on days 1 and 8 (n=37) or NIAT alone (n=38). Median times to last follow-up were 17.0 (interquartile range, 12...
June 27, 2016: Journal of the American Society of Nephrology: JASN
K Dahan
Membranous nephropathy (MN) accounts for about 20% of cases of nephrotic syndrome in the adult. Thickening of glomerular capillary walls results from subepithelial formation of immune deposits containing IgG and the membrane attack complex of complement, which is the major mediator of proteinuria, and antigens. Idiopathic forms of MN (IMN) represent 70 to 80% of all cases. A major breakthrough was the identification of the podocyte antigen PLA2R as the target of circulating antibodies in about 70% of IMN, which confirmed that the disease was auto-immune in nature...
May 25, 2016: La Revue de Médecine Interne
Qiu-Hua Gu, Zhao Cui, Jing Huang, Yi-Miao Zhang, Zhen Qu, Fang Wang, Xin Wang, Su-Xia Wang, Gang Liu, Ming-Hui Zhao
Patients with combined membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) have been reported with different clinical significance. Investigations on the possible mechanisms of the combined glomerular lesions are necessary but scarce. Twenty patients with both MN and FSGS lesions were enrolled in the study. Sixty-five patients with primary MN and 56 patients with primary FSGS were used as disease controls. Clinical data on renal biopsy and during follow-up were collected. Circulating anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R expression, IgG4 deposition, and soluble urokinase receptor (suPAR) levels were detected...
May 2016: Medicine (Baltimore)
Hong-Rui Dong, Yan-Yan Wang, Xiao-Hong Cheng, Guo-Qing Wang, Li-Jun Sun, Hong Cheng, Yi-Pu Chen
BACKGROUND AND OBJECTIVES: The research work in the past years showed that detection of phospholipase A2 receptor (PLA2R) antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN) was useful for the differentiation between primary MN (PMN) and secondary MN (SMN), but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN), 26 patients with hepatitis B virus-associated MN (HBV-MN), 2 patients with malignancy-associated MN (M-MN) and one patient with IgG4-related MN (IgG4-MN)...
2016: PloS One
Xin Li, Dong Wei, Zhanmei Zhou, Baoguo Wang, Ya Xu, Jie Pan, Chunli Yang, Jie Lu, Yurong Qiu
BACKROUND ~This study used two standardized methods to evaluate anti-PLA2R antibody in serum of primary membranous nephropathy (PMN) among Chinese patients to determine  Anti-PLA2R antibody distribution and whether immunological reactivity reflected by antibody titer correlates with kidney function parameters. MATERIAL AND METHOD ~Overall, 82 subjects with biopsy-proven primary membranous nephropathy (PMN) , 22 cases with secondary membranous nephropathy (SMN), 40 non-MN patients with established glomerulonephritis, 20 healthy volunteers were recruited from the Division of Nephrology, Nanfang Hospital, China...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Stéphane Bally, Hanna Debiec, Denise Ponard, Frédérique Dijoud, John Rendu, Julien Fauré, Pierre Ronco, Chantal Dumestre-Perard
Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Measurement of mannan binding lectin (MBL) antigenic level and activity revealed MBL deficiency...
May 6, 2016: Journal of the American Society of Nephrology: JASN
Jean M Francis, Laurence H Beck, David J Salant
Lessons from an animal model that faithfully resembles human membranous nephropathy (MN) have informed our understanding of the pathogenesis of this organ-specific autoimmune disease and common cause of nephrotic syndrome. After it was established that the subepithelial immune deposits that characterize experimental MN form in situ when circulating antibodies bind to an intrinsic podocyte antigen, it was merely a matter of time before the human antigen was identified. The M-type phospholipase A2 receptor 1 (PLA2R) represents the major target antigen in primary MN, and thrombospondin type 1 domain-containing 7A (THSD7A) was more recently identified as a minor antigen...
July 2016: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Shi-Yao Wei, Yu-Xiao Wang, Jian-Si Li, Shi-Lei Zhao, Tian-Tian Diao, Yu Wang, Chang Wang, Ying Qin, Yang Cao, Qiuju Wei, Bing Li
BACKGROUND: M-type phospholipase A2 receptor (PLA2R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA2R (gPLA2R) and the associations of serum anti-PLA2R antibody (sPLA2R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. METHODS: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months...
2016: American Journal of Nephrology
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