Clinicopathologic Features And Prognosis Of Adult Atypical Membranous Nephropathy

Idiopathic membranous nephropathy(IMN)is an immune complex mediated glomerular disease.It is reported that the incidence of MN has been on the rise in the past decades,MN has become the fastest growing disease in the proportion of primary glomerular diseases and one of the main causes of chronic kidney disease.MN is classified as idiopathic membranous nephropathy(IMN)or secondary membranous nephropath(SMN)depending on whether or not it is possible to find an aetiology responsible for it.In clinical,there is a kind of MN diagnosed as atypical membranous nephropathy(AMN).The pathological manifestations of AMN are similar to SMN.In addition to glomerular basement membrane thickening and subepithelial immune complex deposition,SMN pathological manifestations are also accompanied by glomerular mesangial cells and mesangial matrix hyperplasia.In addition to immunoglobulin IgG and complement C3 deposition,IgA,IgM and other parts of the immunoglobulin deposition and even "full house" phenomenon can also be seen in immunofluorescence.SMN may secondary to chronic viral hepatitis B,autoimmune diseases,tumors and so on,while AMN has not found clinical evidence of secondary cause at present.The exact definition and classification of AMN are still controversial,and there are relatively few large-scale studies on its pathogenesis and prognosis.Researchers found M-type phospholipase A2 receptor(PLA2R)and anti-PLA2R antibody in 2009 and indicated that PLA2R antigen and IgG4 were found to be co-located in subepithelial deposits.It has been reported that mostly circulating anti-PLA2R antibody are significantly correlated with the disease’s clinical activity and with response to treatment.However,the significance of anti-PLA2R antibody in the pathogenesis and clinical treatment of AMN remains unclear.This study was grouped by etiology and retrospectively analyzed the characteristics of membranous lupus nephritis,HBV-MN and undetermined atypical membranous nephropathy.And then according to the result of serum anti-PLA2R antibody,the patients of undetermined atypical membranous nephropathy divided into two groups to investigate the clinical significance of PLA2R in undetermined atypical membranous nephropathy.MethodsFrom Jan 2015 to Dec 2018,85 cases diagnosed by kidney puncture biopsy in the first hospital of Zhengzhou university were included into the study.A total of 61 patients met the inclusion criteria after screening.Clinical and pathological characteristics were analyzed.Baseline data and follow-up data were collected,and the clinicopathological characteristics and prognosis of the two groups were analyzed and compared.According to the biochemical indexes and clinical manifestations,we analyzed the pathogenic causes and clinical characteristics of the patients.According to the result of serum anti-PLA2R antibody,the patients of AMN group divided into two groups.The clinical,pathological and prognostic differences of AMN patients in the two groups were compared.Results(1)There were 12 patients in anti-PLA2R antibody positive group and 37 patients in anti-PLA2R antibody negative group in AMN group.There was no significant difference between the two groups in gender,mean age of onset,clinical manifestations,smoking history and urban-rural ratio.(2)Compared with anti-PLA2R antibody negative group,serum albumin was lower than anti-PLA2R antibody positive group,which showed significant statistical differences among the two groups.The 24h urinary protein quantification,total cholesterol were higher than those in anti-PLA2R antibody positive group(P=0.032,P=0.031).There were no significant differences in blood urea nitrogen,creatinine,urea acid,erythrocyte sedimentation rate,C-reactive protein,D-dimer between two groups.(3)Compared with anti-PLA2R antibody negative group,the integrals of interstitial inflammatory cell infiltration were more in anti-PLA2R antibody positive AMN group(P=0.018).The positive rate of IgG4 deposits on glomeruli in anti-PLA2R antibody positive group were higher than anti-PLA2R antibody negative group(P=0.024).There were no significant differences in IgG1-3 deposits on glomeruli between two groups.(4)There were 6 patients who chose tacrolimus combined with glucocorticoid for treatment in anti-PLA2R antibody positive group and 17 in the anti-PLA2R antibody negative group.After 12 months of treatment,the complete remission rate of the anti-PLA2R antibody positive group were higher than that of the anti-PLA2R antibody negative group(P=0.045).The most common adverse reactions were elevated uric acid and infection.There was no significant difference in total adverse reactions between the two groups.Conclusions(1)In adult AMN patients,the titer of serum anti-PLA2R antibody is related to the severity of proteinuria and hypoproteinemia.(2)The dominant IgG subclass deposits on glomeruli in anti-PLA2R antibody positive AMN patients group was IgG4.(3)Tacrolimus combined with glucocorticoid more efficient in anti-PLA2R antibody positive AMN patients group in long-term treatment.(4)For patients with serum anti-PLA2R antibody positive,renal biopsy should be performed to clarify the pathological type.