The Level Of Serum Uric Acid And Ischemic Lesion In IgA Nephropathy

Background and ObjectiveIgA nephropathy(IgAN) is the most common form of glomerulonephritis in the world,and is also the main cause of end stage renal disease.IgAN is often accompanies hyperuricemia,Epidemiological studies have found that the incidence of IgAN with hyperuricemia is about29.0%-37.9%. This study retrospectively analyzes clinical and pathological characteristics of144cases of IgAN patients which are diagnosed in our hospital,we assess the Impact of hyperuricemia on IgAN,observe the expression of CD34, CD105, Snail and GLUT9in the kidney, investigate the role of glomerular ischemic lesions and peritubular capillary lesions in the pathogenesis of hyperuricemia renal damage and the possible mechanism of IgAN which is complicated with hyperuricemia.Subjects and methodsClinicopathological data from144biopsy-proven IgAN cases in Tianjing Medical University General Hospital between November201land November2013are studied retrospectively. All except the allergic purpura, systemic lupus erythematosus, HIV infection, cirrhosis,Ankylosing spondylitis and other secondary IgA nephropathy, and they are in accordance with the following characteristics:1age≤40years;2Creatinine clearance rate>90ml/min, blood lipids are no exception, patients were divided into the normal uric acid group and the hyperuricemia group (hyperuricemia diagnostic criteria:Men and postmenopausal women>420umol/L,premenopausal women>357umol/L)according plasma uric acid levels.Morphological changes were evaluated with Oxford classification scoring system and semiquantitive method According to Katafuchi.We Compare clinical and pathologic data in different level of blood uric acid,analysis the relationship between serum uric acid and renal ischemic lesion and the risk factors of ischemic lesion of glomerular. We choose20cases of patients from in the hyperuricemia group,30patients from normal blood uric acid group randomly.The expression of CD34, CD105, Snail, GLUT9are detected by immunohistochemical SP method.We also calculate the capillary density of peritubular capillary according to the CD34and analyze the relationship between serum uric acid and CD34, CD105, Snail, GLUT9.Resultsl.The incidence rate of glomerular ischemic lesions in IgAN which are complicated with hyperuricemia (80%) is significantly higher than that of normal uric acid group (35.1%),x=19.402, P<0.05; when IgA blood uric acid in IgAN patients is above360umol/L level, the incidence of glomerular ischemic lesions is significantly increased, and with the increase of serum uric acid level, the incidence of glomerular ischemic lesions have also increased.2.According to Katafuchi semi quantitative,vascular lesions integral in hyperuricemia group of IgAN patients is significantly higher than that of normal uric acid group (P<0.05).Hyperuricemia group of vascular wall thickening score≥1prevalence rate(86.6%) was significantly higher than that of normal uric acid group(54.3%),=9.10, P<0.05; hyperuricemia group hyalinization score≥1prevalence rate (40%) was significantly higher than that of normal uric acid group (21.9%),=5.208, P<0.05.3.According to Katafuchi semi quantitative,glomerular global glomerulosclerosis, tubular atrophy, interstitial fibrosis in IgAN patients with hyperuricemia group are significantly higher than the normal uric acid group (P<0.05), and between the of mesangial proliferation, balloon adhesion/minutissima crescent, segmental glomerulosclerosis, interstitial infiltration of inflammatory cells in two groups have no significant difference (P>0.05).).According to the Oxford pathological type, the incidence of tubular atrophy, interstitial fibrosis,vascular lesions and glomerulosclerosis and ischemia hardening in hyperuricemia group are significantly higher than the normal uric acid group (P<0.05).4. The Logistic multivariate regression analysis showed that plasma uric acid at the time of renal biopsy is exact risk factors associated with glomerular ischemic lesions (P<0.05).The Spearman correlation analysis showed that, serum uric acid level correlated significantly with the percentage of ischemic lesion of glomeruli, correlation index r=0.543, P<0.05.5.CD34is mainly expressed in the cytoplasm and cell membrane of vascular endothelial cells, neovascular endothelial cells and mature blood vessels were positive, infected endothelial cells were brown, in the form of branched, sinusoidal and spore shape (no lumen); CD105is mainly expressed in the cytoplasm and cell membrane neovascular endothelial cells, endothelial cells were stained brown yellow, in the form of round or mosaic, part of them are no lumen. CD105does not expressed in part of renal tissue,But occasionally can be expressed in renal tubular epithelial cells. Snail is mainly expressed in the nucleus of renal tubular epithelial cells, but weakly expressed in cytoplasm, the nucleus is deep brown, cytoplasm is light yellow, There is high expression in epithelial cells of renal tubule in hyperuricemia group, Snail is not expressed in glomerular; GLUT9mainly expresses in the basement membrane and apical membrane of renal tubular epithelial cells, brownish yellow, There is no or weak expression in the nucleus, blue or pale yellow. More GLUT9expresses in renal tubular epithelial cells of hyperuricemia group, GLUT9is not expressed in glomerular.6.1n the tubular region, compared with the normal uric acid group, average optical density of CD34, CD34positive area percentage of vision area, proximal peritubular capillary density, distal tubular capillary density,peritubular capillary in hyperuricemia group are significantly decreased, the difference was statistically significant (P<0.05);CD105average optical density hyperuricemia group increases significantly,there is statistically significant differences (P<0.05)7. Serum uric acid and CD34average optical density (R=-0.622, P<0.05),CD34positive area percentage of vision area (R=-0.441, P<0.05),proximal peritubular capillary number (R=-0.573, P<0.05), distal peritubular capillary number (R=-0.488, P<0.05),peritubular capillary (R=-0.485, P<0.05) are negatively correlated; blood uric acid and average optical density of CD105(R=0.689, P<0.05)are positively correlated.8. The percentage of ischemic glomerulosclerosis in renal biopsy glomerular and proximal tubular capillary number (R=-0.386, P<0.05), the number of capillaries around the distal tubule (R=-0.372, P<0.05) are negatively correlated; glomerulosclerosis of percentage of glomeruli and Snail positive area percentage of vision area (R=0.415,P<0.05) are positively correlated.9.1n the tubular region, compared with the normal uric acid group,average optical density of Snail,Snail positive area percentage of visual field area increased significantly, the difference was statistically significant(P<0.05), blood uric acid and average optical density of Snail (R=0.504, P<0.05), Snail positive area percentage of visual field area (R=0.582, P<0.05) are positively correlated.lO.In the tubular region, compared with the normal uric acid group, average optical density of GLUT9in hyperuricemia group increases significantly, the difference was statistically significant (P<0.05) between the two groups,GLUT9positive area percentage of vision area has no significant difference (P>0.05),.Serum uric acid and average optical density of GLUT9(R=0.408, P<0.05)are positively correlated.Conclusion1.Hyperuricemia may lead to glomerular ischemia lesion and tubulointerstitial injury.2.Hyperuricemia is closely related to IgAN peritubular capillaries reduction, may induce the expression of Snail in renal tubular interstitiumand result in renal tubulointerstitial fibrosis.3.IgA nephropathy with hyperuricemia may be associated with the increased expression of GLUT9related.