Progress on the M-type phospholipase A2 receptor in idiopathic membranous nephropathy

Objective To highlight current knowledge about M-type phospholipase A2 receptor （PLA2R） which is the first human autoantigen discovered in adult idiopathic membranous nephropathy.Data sources Relevant articles published in English from 2000 to present were selected from PubMed.Searches were made using the terms ＂idiopathic membranous nephropathy,M-type PLA2R and podocyte.＂ Study selection Articles studying the role of M-type PLA2R in idiopathic membranous nephropathy were reviewed.Articles focusing on the discovery,detection and clinical observation of anti-PLA2R antibodies were selected.Results M-type PLA2R is a member of the mannose receptor family of proteins,locating on normal human glomeruli as a transmembrane receptor.The anti-PLA2R in serum samples from MN were primarily IgG4 subclass.Technologies applied to detect anti-PLA2R autoantibody are mainly WB,lIFT,ELISA and so on.Studies from domestic and overseas have identified a strongly relationship between circulating anti-PLA2R levels and disease activity.Conclusion Recent discoveries corresponding to PLA2R facilitate a better understanding on IMN pathogenesis and may provide a new tool to its diagnosis,differential diagnosis,risk evaluation,response monitoring and patient-specific treatment.

Renal Phospholipase A2 Receptor and the Clinical Features of Idiopathic Membranous Nephropathy

Background： According to the renal phospholipase A2 receptor （PLA2R） immunohistochemistry, idiopathic membranous nephropathy （iMN） could be categorized into PLA2R-associated and non-PLA2R-associated iMN. This study aimed to examine whether the non-PLA2R-associated iMN had any difference in clinical features compared with PLA2R-associated iMN. Methods： A total of 231 adult patients diagnosed as iMN were recruited to this retrospective study. Renal PLA2R expression was examined by immunofluorescence. Among these patients, 186 （80.5%） with complete baseline clinical data were used for further study. Urinary protein excretion, serum albumin, and creatinine were analyzed. For those patients with follow-up longer than 1 year, the relationship between PLA2R and response to immunosuppressants were analyzed. The t-test was used for parametric analysis and the Mann-Whitney U-test was used for nonparametric analysis. Categorical variables were described as frequencies or percentages, and the data were analyzed with Pearson＇s Chi-squaxe test or Fisher＇s exact test. Results： Of the 231 iMN patients, 189 showed renal detectable PLA2R expression （81.8%）. The baseline serum creatinine, serum albumin, and urine protein excretion were not significantly different between PLA2R-associated （n = 145） and non-PLA2R-associated iMN patients （n = 41）. However, about 1/3 of the non-PLA2R-associated iMN had abnormal serological tests, significantly more common than PLA2R-associated iMN （31.7% vs. 8.3%, P = 0.000）. The non-PLA2R-associated iMN had lower C4 levels compared with PLA2R-associated iMN （P = 0.004）. The non-PLA2R-associated iMN patients also showed a better response to immunosuppressants （complete remission [CR] 42.9%; partial remission [PR] 14.3%） compared with PLA2R-associated iMN （CR 3.2%; PR 48.4%, P = 0.004） at the 3rd month. Conclusions： There were no significant differences in serum creatinine, albumin, and urine protein excretion between PLA2R-associated and non-PLA2R-associated iMN, while the non-PLA2R-associated iMN patients showed more abnormal serological tests. The non-PLA2R-associated iMN seemed to respond more quickly to the immunosuppressive therapy compared with P LA2R-associated iMN.

Idiopathic membranous nephropathy in children:A case report

BACKGROUND Minimal change disease is a common cause of nephrotic syndrome(NS) in children and has a good prognosis. Idiopathic membranous nephropathy(IMN), a rare cause of NS in children, may progress to chronic kidney disease. However, there is little data on how to evaluate and treat IMN in children.CASE SUMMARY In this article, we report the case of a 7-year-old boy with steroid-resistant NS. After cyclophosphamide pulse therapy combined with oral prednisone, the urinary protein results remained positive. Renal biopsy confirmed the pathological diagnosis of stage Ⅱ MN, with positivity for phospholipase A;receptor. Other immunological and infectious diseases relevant to secondary MN were ruled out by laboratory tests. Subsequently, tacrolimus plus prednisone was administered, and the therapeutic effect was satisfactory.CONCLUSION IMN is rare in children. The main clinical manifestation is NS. The diagnosis depends on renal biopsy. There is little evidence-based data on the treatment of IMN in children. Therefore, large-sample randomized controlled trials need to be performed. Individualized treatment should be used to improve the prognosis of the disease.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy:A case report

BACKGROUND About 70%-80%of patients with primary membranous nephropathy(MN)have phospholipase A2 receptor(PLA2R)in renal tissue.Systemic light-chain(AL)amyloidosis is the most common type of amyloidosis.MN complicated with amyloidosis is rare.CASE SUMMARY A 48-year-old Chinese male presented with nephrotic syndrome,positive serum PLA2R antibody,and positive serum and urine IgG-lambda type M-protein,with a normal ratio of serum-free light-chain level.The patient was diagnosed with MN accompanied by AL amyloidosis.He was treated with rituximab with glucocorticoids and CyBorD regimen of chemotherapy.After 21 mo of follow-up,the patient achieved complete remission regarding nephrotic syndrome without adverse effects of chemotherapy.CONCLUSION We report a case of PLA2R-related MN complicated with primary AL amyloidosis only with renal involvement and successfully treated with rituximab,glucocorticoids and chemotherapy.