Renal Expression And Urinary Excretion Of Hepatocyte Growth Factor In Children With Henoch-Schonlein Purpura

Background and objective:It is well known that Henoch-Schonlein purpura(HSP) is a systemic abnormal reactive vasculitis,and renal function failure induced by progressive Henoch-Schonlein purpura nephropathy(HSPN) is the primary cause of the mortality.However,the exact pathogenesis of HSPN remains unknown,and no unified and effective medicine have been found to heal HSPN.Increasing evidences indicate that there are many kinds of cytokines in the kidney,these cytokines restrict each other,keep balance,and maintain the kidney in a relatively stable condition,but in morbid state,some cytokines express abnormally and the stable internal environment and metabolism are destroied,this may relate to the development and progression of HSPN closely.Recent studies show that hepatocyte growth factor(HGF) is a pleiotropic renal nutrition factor,which has mitogenic,morphogenic,anti-apoptotic and anti-inflammatory activities.Both in vivo and in vitro studies have demonstrated that HGF can repair the damage of renal tissue,regulate the production and degradation of extracellular matrix(ECM) and protect against the renal tissue hypoxia and the development of renal fibrosis in various renal diseases,such as acute renal failure, diabetic nephropathy and renal fibrosis.However,the biological role of HGF in children with HSP and HSPN largely remains unknown.In this study,we examined the urinary excretion and renal expression of HGF in HSP children,discussed the relation between the expression of HGF and the renal histomorphology of HSP and explored the role of HGF in the development of HSPN.Our results suggest novel approaches for the early diagnosis and accurate evaluation of HSPN progression.Methods:1.Subjects:Our study included 78 patients who had been diagnosed with HSP and 26 healthy children as the control.Based on the urinary albumin excretion rate(UAER) in the acute phase,the HSP children were divided into three groups.GroupⅠ(the normoalbuminuria group,N = 38),groupⅡ(the microalbuminuria group,N=24),and groupⅢ(the macroalbuminuria group,N=16).Recovery-phase urine samples were obtained for some of the patients,which included 15 children from groupⅠandⅡ(further classified as groupA) and 5 children from groupⅢ(further classified as group B).Among the above 78 patients,22 received renal biopsy in the acute phase,including five children from groupⅠ,nine children from groupⅡ,and eight children from groupⅢ. The control kidney samples were taken from the normal portions of nephrectomy specimens of patients who underwent surgery due to trauma.2.Urinary HGF excretion was determined by ELISA.3.Renal pathology observation:The nephridial tissues were stained by HE and PAS seperately,then observed by a light microscope.The semiquantitative score was used in the grading of glomeuli and tubulointerstitial pathologic change degree.4.HGF expression in renal tissues:Immunoenzymic-SABC method was applied,then film reading was viewed by LEICA Qwin V3 image processing system and Image-Pro plus software was used to determine the integral optical density(IOD) of HGF exression.5.Statistical methods:Software used:SPSS 16.0 Data representation:x±SDComparison among control group and HSP groups:one-way ANOVA(P＜0.05) Comparison among acute-phase,recovery-phase and control groups: paired or unpaired Student' s t-testAssociation between the urinary HGF level and the renal HGF expression, and the score of renal pathologic change and the renal HGF expression: linear correlation analysisResults:1.The urinary HGF level in acute phaseCompared with the control group,the urinary HGF level was increased in both groupⅠ(P＜0.05) and groupⅡ(P＜0.01),and the increase was more obvious in groupⅡ(P＜0.01,groupⅠvs.groupⅡ).Urinary HGF was lower in groupⅢcompared with groupⅠ(P＜0.01) or groupⅡ(P＜0.01).No statistical difference was observed between groupⅢand control group(P＞0.05).2.The urinary HGF level in recovery phaseFor group A,the urine HGF level in recovery phase was lower than in acute phase(P＜0.05),but not statistically different with the control group(P＞0.05).For group B,the urinary HGF level in recovery phase was significantly higher compared with both acute phase(P＜0.01) and control group(P＜0.05).3.The HGF expression in kidneyNone or little HGF was expressed in the renal tissues of the controls while much more HGF was apparently expressed in the HSP patients.The IOD of HGF staining was higher in groupⅡthan that in both groupsⅠ(P＜0.05) andⅢ(P＜0.01).Meanwhile,no statistical difference of IOD was found between groupⅠand groupⅢ(P＞0.05).4.The correlation between urinary HGF level and renal HGF expressionThe linear correlation analysis revealed a tight correlation between urinry HGF level and renal HGF expression(R=0.71,P＜0.01).5.The correlation between the score of pathological changes and the expression of HGF in glomeruli.In the glomeruli of which pathological changes grade one and two, the linear correlation analysis revealed a positive correlation between the score of pathological changes and the HGF expression(n=19, r=0.49,p=0.03).In glomeruli of which the pathological changes grade three,the linear correlation analysis revealed no statistical correlation between the score of pathological changes and the HGF expression(n=3,p=0.26).6.The correlation between the score of pathological changes and the expression of HGF in renal tubule and interstitiumIn the renal tubule and interstitium of which pathological changes grade one and two,the linear correlation analysis revealed a positive correlation between the score of pathological changes and the HGF expression(n=18,r=0.85,p=0.00).In renal tubule and interstitium of which the pathological changes grade three,the linear correlation analysis revealed no statistical correlation between the score of pathological changes and the HGF expression(n=4,p=0.38).Conclusion:1.HGF is involved in the development and progression of HSPN.In the initial stage of renal involvement in HSP children,the renal production of HGF is increased to provide protection.However,when the renal injury progress further,the HGF production will decrease.2.No matter in glomeruli or renal tubule and interstitium of which pathological changes grade one and two,the expression of HGF increased with the progression of the pathology.This result reveals that HGF is involved in the initial pathologic progression of both glomeruli and renal tubule and interstitium in children with HSPN. 3.The level of urinary HGF can not only reflect the expression of renal HGF in HSP patients,but also represent the severity of the renal injury to some extent.4.The urinary HGF level is increased with UAER in normoalbuminuria and microalbuminuria HSP children,but when the UAER is increased to the macroalbuminuria stage,the urinary HGF excretion will decrease.5.The urinary HGF levels in children with mild nephropathy can recover to the normal levels in parallel with the improvements of the clinical symptoms.However,in the children with severe nephropathy the urinary HGF excretion will increase in the recovery phase and go even higher than the control level.6.The detection of urinary HGF in HSPN children would be a non-invasive and effective way to evaluate the state and the prognosis of the disease.