Expression Of NGAL In The Renal Tissue Of Patients Of IgA Nephropathy With Tubulointerstitial Damage

Objective: Renal fibrosis represents the final pathway that leads to end-stage renal failure for many species of chronic renal disease. Tubulointerstitial fibrosis (TIF) is one of characteristics with renal sclerosis. Tubulointerstitial fibrosis is multifactorial, and includes activation of tubule stromal cells, inflammatory cells infiltration(lymphocytes and mononuclear macrophage), vasoactive substance,overexpression of resulting to fibrosis cytokine and deposition of extracellular matrix(ECM).Moreover positive interventions may block or reverse TIF before histology can retroconversion.The lately researches found that neutrophil gelatinase-associated lipocalin(NGAL) can prevent the process of renal interstitial fibrosis and delay the progression of the chronic renal disease. This text wants to detect the expression of NGAL in the renal tissue of IgA nephropathy with different degree of pathological change, and the relationship between the expression and pathological change was analyzed to explore the significance of NGAL in the progression of IgA nephropathy and to provide theory for clinical treatment.Methods: This study was approved by the Department of Nephrology, the second hospital of Hebei Medical University. We choose 36 cases of IgA nephropathy(25 males and 11 fema- les).The mean age of them was 35.0±12.6 years.They were defi- nited by renal biopsy from July 2008 to Feb.2009.Patients with hypertension, diabetes mellitus, Lupus Nephritis, HBV-GN associated glomerulonephritis,thyropathy,renal damage induced by polyarthritis destruens,neoplasms associated nephropathy and those on glucocorticoid,immunosuppressive agents,enoxa- parin sodium and angiotensin converting enzyme inhibitor be- fore renal biopsy were excluded from this study. 5 specimens as control group(2 males and 3 females,the mean age was 50.4±11.0 years) were collected from the normal renal tissue apart from kidney tumor.All tissues were diagnosed as normal which evaluated by lighe microscopy and immunofluorescence.IgA nephropathy patients were divided into 3 groups by Lee's classical definition:mild pathological change group(6 cases, Lee gradeⅠ,Ⅱ),midrange pathological change groups (Lee gradeⅢ,Ⅳ) and severe pathological change group(Lee gradeⅤ).For NGAL expression in kidney tissues,immunohistochemical staining was used for normal portions of kidneys and kidneys with IgA nephropathy.The semiquantitative analysis of renal tissue immunohistochemistry were analyzed.Collecting detailed clinical and pathological datas. Then the expression of NGAL was analyzed with clinical and pathological datas.Result: 1Clinical data: With the aggravation of tubulointer- stitial damage, Upro in severe pathological change group was obviously higher than in mild and midrange pathological chan- ge groups(P<0.01).At the same time,Ccr,serum ALB and uosm decreased obviously.2 The rate of glomerulosclerosis in severe pathological change group was obviously higher than in mild and midrange pathological change groups(P<0.01). 3 Hemiqua- titate score was used for tubulointerstitial damage. The index of tubulointerstitial damage in mild pathological change group was 0. There was no significant difference between mild pathologi- cal change group and control group.The index of tubulointersti- tial damage in midrange and severe pathological change group was higher than mild pathological change group (P<0.01).4 NGAL was mainly expressed in endochylema of proximal convoluted tubular epithelial cell in renal biopsies from normal kidneys and IgA nephropathy.No expression in glomeruli, renal interstitium and inflammatory cells. In renal biopsies from normal kidneys, NGAL expression was barely detectable.With the progression of tubulointerstitial damage, the expression of NGAL increased gradually. There was significant differrence between control group and IgAN groups (P<0.01).But it was not different between mild and midrange pathological chang groups (P>0.05).With the aggravation of tubulointerstitial damage, renal interstitium fibrous, renal tubule atrophia and inflamma- tory cells infiltration were increaseed. The expression of NGAL decreased gradually.It was significant different between severe pathological change group and mild, midrange pathological chang groups (P<0.01). 5 A significant negative correlation was found between the expression of NGAL and the rate of glomerulosclerosis(r=﹣0.575;P<0.01) in IgA nephropathy.And the index of tubulointerstitial damage also had negative correla- tion with the expression of NGAL(r=﹣0.693;P<0.01).The de- crease of NGAL expression had positive correlation with the decrease of urine osmotic pressure,serum ALB and Ccr (r=0.494, 0.474,0.601;P<0.01);negative correlation with Upro(r=﹣0.482; P<0.01).No correlation was found between the expression of NGAL and serum cholesterol, serum IgA in IgA nephropathy.Conclusion: 1 NGAL was mainly expressed in endochy- lema of proximal convoluted tubular epithelial cell in renal tissue from normal kidneys and IgA nephropathy.2 In renal tissue from normal kidneys, the expression of NGAL could be detected a little.With the aggravation of tubulonterstitial damage, NGAL expression was increased in renal biopsies from IgA nephropathy patients. But NGAL expression was decreased in severe pathological change group.And it had positive correlation with urine osmotic pressure and Ccr.3 NGAL in IgA nephropathy may be a protective factor to meliorate the degree of tubulointerstitial fibrosis.