Significance And Expression Level Of PDGF-D,TIMP-1in Patients Of Iga Nephropathy

Objective: IgA nephropathy is a kind of glomerulonephritis.Its mainfeatures is immune complex deposites on the glomerular mesangium. Theprolifering of mesangial cells and extracellular matrix(ECM) is the basicalhistological change.It is one of the major reasons of glomerulosclerosis andend-stage renal disease(ESRD),As we all known, renal interstitial fibrosis hasclosely correlation with the disbalance of extracellularmatrix (ECM) formedand degradated, which induces a series of clinical and pathophysiologicalchanges.Platelet-derived growth factor (PDGF) family is a major mitogen inforegone polypeptide growth factors, It participates the development of renaldisease by enhancing the genaration and transdifferentiation of mesangialcells and accumulation of extracellular matrix. It has four subunits A, B, Cand D．A large number of experiments had verified the roles of PDGF-A andPDGF-B in various of renal diseases.PDGF-D is a new member which wasdiscovered in2001. Few studies about PDGF-D in IgAN were reported.matrix metalloproteinases (MMPs) can degradate various extracellularmatrix,tissue inhibitor of metalloproteinases(TIMPs) is the specific inhibitor ofMMPs. Among these TIMPs, TIMP-1is the main inhibitor of MMP-9,MMP-3and MMP-1.In this studies, we detected the expression of PDGF-Dand TIMP-1in urine and Serum of patients with IgAN, and analyzed thecorrelation with IgAN, explored the significance of PDGF-D and TIMP-1inthe progression of IgAN, and to provide theory for treatment and preventionof the clinical renal fibrosis.Methods: Twenty-seven patients cases (male twelve, female fifteen,mean age36.00±11.14) diagnosed as primary IgA nephropathy by renalpathoiogy at the second hospital of Hebei medical university were involved inthis study. All patients were not used glucocorticosteroid, ARB, ACEI, cytotoxic drug. exclude lupus nephritis, henoch-schonlein nephritis, hepaticcirrhosis glomerulopathy, HBV-GN associated glomeruloneohritis and so on.IgA nephropathy were devided into three pathological groups by Oxfordclassification of IgA nephropathy in2009(mild pathological change group T00%～25%; moderate pathological change group T126%～50%; severepathological change group T2>50%). Seven healthy cases(male three, femalefour,mean age35.7±15.2)were normal control group.Expression of PDGF-Dand TIMP-1in urine and serum were detected by ELISA.Collecting clinic-aldatum:age,24hour urinary protein quantitative(Upro),serum albumin(ALB),serum creatinine(Scr)and blood urea nitrogen(BUN).Then the expression ofPGDF-D and TIMP-1were analyzed with clinical datum.The data wereanalyzed by SPSS13.0software. All datum were expressed by mean±standarddeviation. Group comparison adopt by analysis of variance and nonparametrictext.Results:1. Clinical datum:With the aggravation of tubulointerstitial damage, Upro andScr were gradually increased from mild pathological change group to severepathological change group(P<0.05)；BUN in moderate and severe pathologicalchange groups was higher than in mild pathological change group(P<0.05);There was no difference between the moderate and severepathological change groups(P＞0.05); Serum ALB in severe pathologicalchange group was lower than in mild and moderate pathological changegroups(P<0.05), There was no difference between the mild and moderatepathological change groups(P＞0.05); At the same time,There was nosignificant difference(P>0.05)with the levels of and age.2. Urinary levels of PDGF-D and TIMP-1: With the aggravation oftubulointerstitial damage, urinary levels of PDGF-D and TIMP-1weregradually decreased from control group to severe pathological change group(P<0.05).3. Serum levels of PDGF-D and TIMP-1: With the aggravation oftubulointerstitial damage, serum levels of PDGF-D were gradually decreased from control group to severe pathological change group (P<0.05).There wasno difference between the control group and mild pathological change groupabout serum levels of TIMP-1, likewise, between the moderate and severepathological change group.Other groups were gradually decreased (P<0.05).4. The correlation between the level of PDGF-D and TIMP-1: The expressionof serum PDGF-D has positive correlation with serum TIMP-1(P<0.05).Theexpression of urinary PDGF-D has positive correlation with urinary TIMP-1(P<0.05).5. The correlation between pathological and clinical datum: The expression ofurinary PDGF-D, urinary TIMP-1, serum PDGF-D and serum TIMP-1haspositive correlation with urinary protein and Scr.The expression of urinaryPDGF-D, urinary TIMP-1, serum PDGF-D and serum TIMP-1has negativecorrelation with serum ALB. The expression of urinearyTIMP-1has positivecorrelation with BUN.Conclusions:1. With the aggravation of tubulointerstitial damage, PDGF-D and TIMP-1inthe serum and urine of IgA nephropathy patients were gradually decreased.These suggested that PDGF-D and TIMP-1participate the developement andprogress of IgA nephropathy.2. With the aggravation of tubulointerstitial damage, urinary protein and Scrof IgA nephropathy patients were gradually decreased. The levels ofPDGF-D and TIMP-1has positive correlation with the levels of urinaryprotein and Scr, which indicate that the levels of PDGF-D and TIMP-1couldreact the severity of the disease.3. PDGF-D and TIMP-1in the serum and urine of IgA nephropathy patientshas positive correlation, which indicate that they may effect with each other inproducing biologic contribution.