Clinical And Pathological Studies Of IgA Nephropathy With Massive Proteinuria

[Background and Objective]Previous studies suggested that proteinuria play a worse role in progression of IgAN.At present,clinicopathologic characteristics correlated with presence of massive proteinuria in IgA nephropathy were unclear,as well as the treatment efficiency of corticosteroids and long-term prognosis.with advances in pathological technology,virtual slides make the measurement of quantitative pathological indicators such as glomerular density,maximal diameter,renal cortical area and interstitial fibrosis area are convenient and possible nowadays.In 2016,the IgAN International Collaborative Group proposed segmental sclerosis subdivision with or without podocyte hypertrophy or tip changes.Therefore,in addition to exploring the clinicopathologic characteristics with massive proteinuria,this study also want to verify the updated 2016 IgAN Oxford classification and to explore the possibility and practicality for evaluating the efficiency of quantitative pathological indicators in IgAN.[method]This study was divided into two parts,the first part retrospectively enrolled patients in January 2003 to October 2015 in our hospital with IgAN presenting with massive proteinuria,follow-up time is greater than 6 months.We analyzed clinicopathologic characteristics,the treatment efficiency of corticosteroids and long-term prognosis with massive proteiuria in IgAN.The second part verified the updated 2016 IgAN Oxford classification.Besides,trying to explore the possibility and practicality for evaluating the efficiency of quantitative pathologicalindicators in IgAN.The pathological sections of the patients were scanned by electron microscopy(Aperio CS2 system scanner).The images were analyzed by Leica Biosystems Image Scale Viewing software.The diameter of glomeruli,glomerular area,cortex area,and interstitial fibrosis area were acquireed directly by inmage software conveniently.Gloumerular density was calculated by the formula of cortical cortical density.[Results]The first part1.A total of 156 cases were enrolled,proliferative lesions were more significantly in this group compared with patients in Oxford study and VALIGA study.Among the baseline characteristics of Oxford classification MEST-C,only crescent lesions correlated with 24hUP,MAP and eGFR level.2.Patients were divided into three groups according to the treatment efficiency with glucocorticoids.Three baseline characteristics including eGFR level,proportion of segmental sclerosis and glomerular density showed significant differences among the three groups.S1 correlated with the annual eGFR decline slope.3.Glomerular density and baseline eGFR were independent indicators for renal survival by multivariate Cox regression model.Treatment efficiency with 6-month-glucocorticoids can indicate long-term prognosis in IgAN.The second part1.Crescent Classification of the updated 2016 Oxford modified was still limited in use in patients with massive proteinuria treated with glucocorticoids.2.The tip lesions or podocyte hypertrophy accompaning S1 in IgAN patients with massive proteiuria showed no higher proteinuria.S1 with podocyte hypertrophy or tip lesions even showed no better prognosis after treatment with glucocorticoids and immunosuppressive agnets,all of which were different from the 2016 Oxford modified validation.3.Quantitative pathological indicators can help to predict the prognosis,GD(<1.99mm2)and interstitial fibrosis percentage(?33.0%)can act as effective indexs for the treatment efficiency with glucocorticoids and long-term prognosis in IgAN,However,maximum glomerular diameter can not work as these.[conclusions]1.Only segment in MEST-C classification can predict the treatment response with glucocorticoids.2.Only baseline eGFR were independent indicators for renal survival by multivariate Cox's regression model.3.The release situation of proteinuria after 6-month treatment with glucocorticoids can predict long-term prognosis on renal survival.4.The practicability of crescent subclassification and the S1 subgroup of the updated Oxford classification need to be verified by further multi-center prospective study.5.GD(<1.99mm2)and interstitial fibrosis percentage(?33.0%)can act as effective indexs for the treatment efficiency and prognosis.6.Glomerular density correlates with 6-month treatment efficiency with glucocorticoids.It can be an independent indicators for renal survival by multivariate Cox's regression model.