Expression And Significance Of Heme Oxygenase-1in The Patients Of IgA Nephropathy

Objective: IgA nephropathy(IgAN) is the commonest primary glomeru-lonephritis in our country, about40percent of the primary glomerulo-nephritis. IgAN is the main reason of chronic renal failure.Many studies haveshowed IgAN were in progressing and have reported that15%~40%ofpatients develop into end-stage renal disease within20~25years from theapparent onset of disease. Not only the glomerular sclerosis, the renal functiondamage, hypertension and the urine protein are related with the IgAN, but alsothe interstitial fibrosis is closed with the prognosis. Tubulointerstitial fibrosisis multifactorial, such as activation of tubulointerstitial cells, flammatory cellsinfiltration (lymphocytes and mononuclear macrophage), vasoactive substance,overexpression of resulting to fibrosis cytokine and deposition of extracellularmatrix(ECM).Moreover positive interventions may block or reverse tubulo-interstitial fibrosis before histology can t retroconversion. Heme oxygen-nase-1(HO-1) was demonstrated to participate, as the first and rate-limitingenzyme, in the conversion of heme into a bile pigment, biliverdin, free ironand carbon monoxide(CO). Then the biliverdin is reduced to bilirubin bybiliverdin reductase.The free iron is combined with ferroprotein.Lots ofstudies show that HO-1possess anti-inflammatory, antiapoptotic, anti-oxidant,and antiproliferative properties. In the renal pathological state, HO-1mainlydistributed the proximal and distal tubule in the renal cortex and medullarycollecting duct epithelial cells.It is considered as a protective factor of kidney,especially closely related to renal vessel and tubular. There is a studydemonstrates that induction of heme oxygenase-1can halt and even revers-e renal tubule-interstitial fibrosis.Recent years,the mechanism of HO-1halteven reverse renal tubule-interstitial fibrosis has become a hot spot in thestudy.The article wants to detect the expression of HO-1in the renal tissue, serum, urinary sediment of IgA nephropathy with different degree of renaltubule-interstitial fibrosis, and the relationship between the expression andpathological, clinical change were analyzed to explore the significance ofHO-1in the progression of IgA nephropathy and to provide theory bases forclinical prevention and treatment.Methods: This study was approved by the department of Nephrolo-gy,the second hospital of Hebei Medical University.We chosen32cases (21males and11females) of IgA nephropathy by renal biopsy diagnosed fromNovember2010to July2011.The mean age of them was35.9±12.0years.Patients with hypertension renal damage, nephritis of Henoch-Sch nleinpurpura, HBV-GN(HBV-glomerulonephritis), Lupus Nephritis, thyropathyassociated glomerulonephritis, renal damage induced by polyarthritis des-truens, neoplasms associated nephropathy,the acute kidney injury induced bymedicine, contrast medium and rhabdomyolysis, interstitial nephritis wereexcluded from this study. The patients were not used glucocorticoid,immunosuppressive agents and statins before renal biopsy.7cases as controlgroup were collected from healthy subjects with normal urine routine, normalliver function and renal function, without cerebrovascular disease, withoutcardiovascular disease, without high blood pressure history and withoutdiabetes mellitus history.According to the Oxford classification of IgAnephropathy in2009, the patients were divided into3groups by the percent ofrenal tubular atrophy/tubulointerstitial fibrosis: mild group T0≤25%, moderategroup T126%~50%, severe grouop T2＞50%.The expression of HO-1in therenal tissue was detected by immunohistochemistry. The expression of HO-1in the serum and urinary sediment was detected by enzyme-linked immune-osorbent assay.The semiquantitative analysis of renal tissue Immuno-histochemistry were analyzed.Clinical parameters included age, bloodpressure, serum uric acid, urinary protein quantitative and estimate glomerularfiltration rate(eGFR). Then the expression of HO-1was correlated analysisedwith clinical and pathological datum. Results:1Clinical datum in IgAN patients: Between T0, T1and T2group, the age wasno statistical significance (P>0.05). Mean arterial pressure, urine protein in T2group were higher than in T0and T1groups (P<0.05). At the same time,eGFR were lower than in T0and T1groups.2In renal tissue of IgA nephropathy, the HO-1express mainly in the proximaland distal tubular epithelial cells, but renal glomerulus and renal interstitialand inflammatory cells do not have exspression.3The expression of HO-1in the renal tissue was statistical significance amongT0, T1and T2groups.The expression of HO-1in the renal tissue of T0groupis higher than the T1and T2groups (P<0.05). Between T1and T2groups, theexpression of HO-1was no statistical significance (P>0.05).4The level of HO-1in the serum of IgA nephropathy is higher than thenormal group (P<0.05).Among T0, T1and T2groups, the level of HO-1in theserum was no statistical significance (P>0.05).5The level of HO-1in the urinary sediment of IgA nephropathy is higher thanthe normal group (P<0.05). Between T0, T1and T2groups, the level of HO-1in the urinary sediment was statistical significance (P<0.05).6Correlation analysis: The expression of the HO-1in the renal tissue hadpositive correlation with eGFR(r=0.383,P<0.05); negative correlation withserum uric acid (P<0.05). The level of the HO-1in the serum had positivecorrelation with mean arterial pressure (r=0.426, P<0.05). The level of theHO-1in the urinary sediment had negative correlation with renal tubuleatrophy percent(r=0.376,P<0.05).Conclusions:1In renal tissue of IgA nephropathy patients, HO-1mainly expressed inproximal and distal tubular epithelial cell cytoplasm. With the aggravation oftubulointerstitial fibrosis and serum uric acid, HO-1expression wasdecreasing in renal tissue of IgA nephropathy patients.2With the aggravation of arterial pressure, HO-1level was increased in serum,has no correlation with the tubulointerstitial fibrosis.3With the aggravation of tubulointerstitial fibrosis, HO-1level was increased in urinary sediment. The urinary HO-1may be a biomarker for evaluatingtubulointerstitial of IgAN.