Expression Of Kidney Injury Molecule-1 In Adult Primary Membranous Nephropathy And Its Clinical Significance

Background and ObjectivePrimary membranous nephropathy(PMN)remains one of the most common causes of nephrotic syndrome(NS)among adults,and at meantime the leading cause of end stage renal failure(ESRD)both in western countries and China as well.As one of the most common pathological type for nephrotic syndrome in adults,there is an increasing trend in the prevalence of PMN.Recent researches showed that PMN would soon pass IgA nephropathy to become the leading type of primary glomerular disease in China.PMN is an organ-specific autoimmune disease.The treatment of PMN consists of immunosuppressive therapy(IST)and conservative therapy.IST has been proved to be effective in increasing the probability of remission of proteinuria and protecting from renal function deterioration.There are still a portion of patients who can't enter remission after taking different types of immunosuppressive agents tend to have poor prognosis.Kidney injury molecule-1(KIM-1)is a type 1 transmembrane glycoprotein,which is expressed in the epithelial cells of the proximal tubule.KIM-1 is specifically expressed in renal proximal tubular epithelial cells,which regenerate after kidney injury.KIM-1 can be cleaved at its ectodomain region to generate a soluble fragment.The soluble fragment which is released into urine can be quantitatively detected by enzyme linked immunosorbent assay(ELISA).The expression of KIM-1 is upregulated in a variety of acute and chronic kidney diseases and is found to be closely correlated with the severity,therapeutic efficacy and long-term prognosis.The present study was aimed to investigate KIM-1 expression levels in urine and renal biopsy tissues in adult PMN patients,analyze the correlation between KIM-1 and clinical indexes,pathological parameters and therapeutic efficacy and discuss the predictive value of urinary KIM-1 level for tubulointerstitial lesion and therapeutic effect.Methods51 biopsy-proven PMN,admitted to the department of nephrology at Qilu Hospital of Shandong University between January 2012 and December 2014 were involved,with their clinical data being collected.Based on the treatment strategy and curative effect,patients were classified into three groups:spontaneous remission(n=18),remission with IST(n=20)and non-remission with IST(n=13).The urine samples of patients and 20 healthy individuals were collected.The concentration of urinary KIM-1 was detected by ELISA and represented as KIM-1/Cr.The renal tissue sections of patients and adjacent non-neoplastic tissues were collected.Immunohistochemistry was used to detect the expression of tissue KIM-1.Retrospective analysis was used in this study to compare KIM-1 levels in each group and analyze the respective correlation between KIM-1 and clinical indexes,pathological parameters,attempting to expound the predictive value of the KIM-1 for tubulointerstitial lesion and therapeutic effect in PMN adult patients.ResultsCompared with healthy subjects,KIM-1 expression was significantly higher in PMN patients.KIM-1 expression in non-remission with IST group was significantly increased than that of spontaneous remission group and remission with IST group.KIM-1 expression positively correlated with 24 hours urinary protein,urinary?2-microglobulin,and the severity of tubulointerstitial lesion.Meantime,it negatively correlated with serum albumin.Urinary KIM-1/Cr predicting poor therapeutic effect by the area under the curve was 0.809(95%CI,0.663-0.954).The urinary KIM-l/Cr levels exerted a gradually increasing trend as tubulointerstitial injury became more severe.Urinary KIM-1/Cr predicting tubulointerstitial injury by the area under the curve was 0.798,better than ?2-microglobulin.There was a significant correlation between urinary KIM-1/Cr and renal KIM-1 levels,with Spearman's rank correlation coefficient of 0.914.ConclusionKIM-1 expression is induced in PMN.Significant correlation was found between urinary KIM-1 and tissue KIM-1.Detection of urinary KIM-1 at an early stage of the disease may be helpful to predict therapeutic effect in adult PMN patients.The urinary KIM-1 level could help to evaluate the severity of tubulointerstitial lesion in adult PMN patients.Compared with the traditional indicator ?2-microglobulin,urinary KIM-1 excretion seemed more sensitive and specific in identifying tubulointerstitial lesion.