Kidney Injury Molecule-1Expression And Significance In The Renal Allograft Injury

Kidney injury molecule-1(KIM-1) is a new specific biomarker of proximal tubule injurythat can be measured both in urine and kidney tissue samples. It is an apoptotic-cellphagocytosis and scavenger receptor that is most highly upregulated in proximal tubularepithelium in acute and chronic kidney injury. Also, much attention has been paid to itspossible pathophysiological role in modulation of tubular damage and repair. In renalallografts, tubular injury associated with ischemia, nephrotoxicity secondary toimmunosuppressive medication, and/or acute cellular rejection can lead to chronic allograftnephropathy and eventual graft failure. Pre-renal and post-renal factors contributing to renalfailure are not always easily distinguished from intrarenal injury in allograft recipients.Changes in kidney epithelial cell morphology in allograft biopsies can vary from no orminimal histologic changes of proximal tubules to diminished brush borders, apoptosis and/ornecrosis, dilated tubules, and sloughed epithelial cells in the tubular lumina. A pathologicdiagnosis of acute tubular injury is often quite subjective. A sensitive tissue biomarker oftubular injury, which can be used to identify or confirm the presence of epithelial cell injurywhen pathological changes are minimal would be very helpful in the evaluation of biopsyspecimens.The topic around the KIM-1as the core of the study, we explore the significance of thechange and its expression in the renal allograft injury.A total of69patients who underwent kidney transplantation between2009-2011wereenrolled in this study. KIM-1expression was detected by immunohistochemical methods andthe association of KIM-1and blood biochemical indexes was analyzed. KIM-1expressionincreased as Banff2007classification grade increased and was positively correlated withtubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1expression was strongly positive in the chronic active antibodymediated rejection group.Interestingly, KIM-1was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group,27.27%(3/11) of the cases withnormal serum creatinine level showed weakly positive KIM-1expression in their renal tissues.KIM-1expression level is positively correlated with renal allograft damage and tubular cellinjury. KIM-1is expressed in tubular epithelial cells before blood biochemical indexesbecome elevated and morphological changes occur. KIM-1expression is an early, sensitive,and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.Serum KIM-1expression was detected by ELISA methods, we explore the significanceof the change and its expression in the renal allograft injury.The results showed that:(1) Theserum KIM-1expression is associated with renal allograft injury.(2) Chronic active rejectioncan occur resulting the serum KIM-1expression, suggesting that graft worsening renalfunction status.(3) Early serum kidney injury molecule-1levels may be the new biochemicalmarker for renal allograft function.In this experimental study, We make use of cyclosporine in renal tubular epithelial injuryin vitro, which produces KIM-1expression and initial exploration of which mechanism tofind drugs which can protect and delay renal allograft injury by cyclosporine.In the experiment, renal proximal tubule epithelial cells was injuryed by cyclosporine invitro, suitable concentration injury screening of cyclosporine was determined by using the MTTassay method; screening using the MTT assay method of drug intervention may improve renalcyclosporine tubular epithelial cell injury; screened erythropoietin (EPO) can protect renaltubular cells. Using mitogen-activated protein kinase system blockers (p38pathway inhibitorSB202190, ERK1/2pathway inhibitor PD98059), blocking the expression of thecorresponding enzyme mechanisms and biochemical processes occurring to speculate. ELISAusing the method of identifying the expression of KIM-1in the cell supernatant, the KIM-1expression level of statistical variation. Characteristics of the cells was measured by flowcytometry apoptosis in renal tubular injury in cyclosporineWhen the renal tubule cell was injured by Cyclosporine, KIM-1expression was increased,in the process of mitogen-activated protein kinase in the p38pathway, ERK1/2pathway playsa role. Blocking these two paths can be reduced HKC CsA-induced apoptosis rate (P <0.05),the ratio of living cells increased (P <0.05), reducing the ratio of necrotic cells (P <0.05), while reducing the KIM-1expression (P <0.05). EPO can be added to reduce the HKC cellsKIM-1protein (P <0.05); optional EPO15U/ml and30U/ml experiment with the effect ofincreasing the amount of EPO may be reduced KIM-1expression, suggesting that EPO mayantagonize CsA on renal epithelial damage, reduce the occurrence of CsA-induced tubularepithelial cell apoptosis and necrosis.Kidney injury molecule-1expression and changes in renal allograft has importantresearch value, could be early、sensitive、specific determination of renal tubular epithelial cellinjury and biochemical marker for renal allograft injury.The serum kidney injury molecule-1levels may become early biochemical markers. When the renal tubule cell was injured byCyclosporine, KIM-1expression was increased, in the process of mitogen-activated proteinkinase in the p38pathway, ERK pathway in which play roles. Blocking the p38pathway,blocking the ERK1/2pathway, adding EPO three factors can reduce the renal tubular cellsKIM-1expression, delaying the effective protection and cyclosporine for transplant renaltubular epithelial damage in the process. The results and conclusions of this topic, for thekidney injury molecule-1in renal transplantation field to provide a favorable basis forexperimental evidence, as well as reducing cyclosporine to continue to explore aspects oftransplant renal injury in experimental models and provide reference effective experimentaldrugs.