Study On Association Between Angiopoietin-Like Protein 4 And Podocyte Injury

Objective:Podocyte injury is an important reason for proteinuria and renal dysfunction,and involve a variety of types of kidney disease,renal pathology in the features of changing the number of podocytes(reduction in the number or density reduction),glomerular basement membrane thickening and podocyte foot process effacement,clinical characteristics are usually of a large number of clinical proteinuria,hypoalbuminemia,hyperlipidemia and edema.Podocyte injury is closely related to immune inflammatory response,circulating factors and lipid metabolism abnormalities.Recent studies showed that angiopoietin-likeprotein-4(angiopoietin-like-4,ANGPTL4)as a non-immune circulating factorinvolved in podocyte injury and the most common researches are in the minimal Change disease(MCD),and participate in negative feedback path about proteinuria and hypertriglyceridemia,and the studies have been verified in animal models and a small amount of clinical trials.The present study was to compare with different pathological types of kidney disease in serum and urine ANGPTL4 content,to explore the differential expression of ANGPTL4 in different kidney disease types including podocyte injury and non-podocyte injury,and to explore the relevance on the ANGPTL4 and clinical laboratory indicators.Methods: The study patients selected from the department of nephrologyin Second Hospital of Hebei Medical University,from February 2015 to November 2015,renal pathology diagnosed as MCD,MN,MsPGN patients with a total of 93 cases,exclusion criteria:purpura nephritis,lupus nephritis,the tumor,blood system diseases,liver diseases;recent history of infection or special materialallergy history;patients with previous diagnosis of chronic kidney disease including dialysis and kidney transplantation;metabolic syndrome,obesity,familialhypercholesterolemia and fatty liver.All patien-ts without the non-steroidal anti-inflammatory drugs,glucocorticoid,cytotoxic drugs or immunosuppressants within 24 hours.According to pathological types divided into:MCD group(including the onset and recurrence),MN group,MsPGN group and control group(MCD patients in complete remission).Serum and urine ANGPTL4 expressionwas detected by ELISA and at the same time collecting clinical indicators of gender,age,24-hour urinary protein,serum albumin,triglycerides,total cholesterol,serum creatinine for correlation analysis.All experimental data are expressed as mean±standard,comparison between the groups using independent samples t-test or analysis of variance if the data in line with the normal distribution homogeneity of variance and non-normal data using rank sum test.Correlation analysis using pearson or spearman correlation.All states analyses were performed using Statistical package for social sciences(SPSS)19.0.Results:1 The clinical data: age and gender between the groups had no significantdifference(P>0.05).24-hour urinary protein excretion of experimental group was significantly higher than the control group(P<0.05).In the experimental group,urinary protein excretion of MCD group compared with MN group was not statistically significant(P>0.05);urine protein of MsPGN group less than MCD and MN group,and had statistical significance(P<0.05).Serum albumin level of experimental group was significantly lower than the control group(P<0.05).In the experimental group,serum albumin levels of MCD group and MN group had no statistically significant differences(P>0.05);serum albumin level of MsPGN group is higher than the MCD and MN group,and had Statistical significance(P<0.05).Total cholesterol level of the experimental group was significantly higher than the control group(P<0.05).In the experimental group,total cholesterol level of MN group had no significant difference with MCD and MsPGN group(P>0.05);MCD group of the total cholesterol level was significantly higher than the MsPGN group(P<0.05).Experimental group of blood triglyceride level was higher the control group(P<0.05).In the experimental group,MCD group of blood triglyceride level was higher than MN and MsPGN group and the differences were statistically significant(P<0.05),MN group of serum triglyceride level was no significant difference with MsPGN group(P>0.05),serum triglyceride level of nephrotic group was significantly higher than non-nephrotic group(P<0.05).Serum creatinine levels between the groups were not statistically significant(P<0.05).2 Serum level of ANGPTL4: The serum ANGPTL4 level of experimentalgroup was lower than the control group(P<0.05).In the experimental group,thedifference among the groups were statistically significant(P<0.05).In the non-nephrotic group,serum ANGPTL4 level of MCD group was the lowest,there isa statistically significant differences with MsPGN group and MCD-remission group(P<0.05),other groups were not statistically significant(P>0.05);In the nephrotic group,the difference among the groups was not statistically significant(P>0.05).3 Urine ANGPTL4 level: The urine ANGPTL4 level of experimental group was higher than the control group(P<0.05).In the experimental group,MCD group of urinary ANGPTL4 level had no statistically significant differencewith MN group(P>0.05);the differences among the other groups had Statistical significance(P<0.05).In the nephrotic group,the urine ANGPTL4 level of MCD group was the highest,MsPGN group of urine ANGPTL4 level was the lowest,differences of the urinary ANGPTL4 level among the groups were statistically significant(P<0.05).4 The relationship of serum ANGPTL4 and clinical indicators:There wasno correlation with the serum ANGPTL4 level and clinical indexes:age,24-hour urinary protein,total cholesterol,triglycerides and serum creatinine.MCD group of serum ANGPTL4 was negatively correlated with serum albumin level(r=-0.389,P<0.05).5 The relationship of urine ANGPTL4 and clinical indicators:There was no correlation with the urine ANGPTL4 level and clinical indexes:age,total cholesteroland serum creatinine.MCD group: The urine ANGPTL4 level was positively correlated with 24-hour urinary protein excretion and serum triglyceride level(r=0.62,r=0.045,P<0.05),and was negatively correlated with serum albumin level(r=-0.54,P<0.05);MN group: The urine ANGPTL4 level was positively correlated with 24-hour urinary protein excretion(r=0.539,P<0.05);MsPGN group: The urine ANGPTL4 level was positively correlated with 24-hour urinary protein excretion(r=0.756,P<0.05),and was negatively correlated with serum albumin level(r=-0.850,P<0.05).Conclusions:In MCD patients,with the increase of proteinuria and reduce serum albumin levels,serum ANGPTL4 secretion increased and further aggravate hypertriglyceridemia,in MN and MCD patients,who podocyte injury,urine ANGPTL4 significantly increased and positively correlated with the level of proteinuria,therefore,urine ANGPTL4 levels may help to assess the degree ofpodocyte injury.