Association of URG11 and Twist with clinical pathological characteristics and prognosis in patients with IgA nephropathy

作者:Du, Rui; Zhao, Lu; Xia, Lin; Liu, Limin; Sun, Wenjuan; Zhao, Ali; Yu, Yan; Han, Hua; Sun, Shiren*
来源:Nephrology Dialysis Transplantation, 2013, 28(9): 2268-2276.
DOI:10.1093/ndt/gft252

摘要

Background. Our previous studies demonstrated that URG11 is involved in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. The objective of this study was to determine the expression levels of URG11 in kidneys with IgA nephropathy (IgAN), and the association of URG11 with various clinical parameters. Methods. We analysed the degree of expression and localization of URG11 in biopsies from kidneys with IgAN, and correlated their immunostaining levels with various clinical and histological parameters. We also analysed the correlation between the expression of URG11 and Twist in the renal interstitium with renal survival. Results. URG11 was strongly expressed in the cytoplasm of tubular epithelial cells obtained from kidneys of patients with IgAN. However, there was little positive staining for URG11 in the renal tubules of normal kidneys (P = 0.024). URG11 protein levels in the tubulointerstitium were inversely correlated with estimated glomerular filtration rates (eGFRs) (r = -0.305, P = 0.038) and the percentage of tubulointerstitial fibrosis (r = 0.350, P = 0.023). Moreover, a high level of URG11 correlated with the activation of Twist expression and E-cadherin repression in patients with IgAN (P = 0.000 and 0.041, respectively). Multivariate analyses indicated that a combination of high URG11 and Twist expression was an independent prognostic factor [relative ratio, RR 4.738 (95% CI: 1.040, 21.591), P = 0.044] of IgAN. Conclusions. Our findings suggest that URG11 staining in renal biopsy specimens might be a novel histological marker for progression in IgAN patients.