Background/aims: Our previous studies indicate that Twist plays important roles in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. However, the expression and clinical significance of Twist in patients with chronic kidney disease are not clear.
Methods: We analyzed the degree of expression and localization of Twist in renal biopsies from a wide variety of hypoxic kidney diseases and correlated their immunostaining scores with clinical and histologic parameters. In particular, we also retrospectively analyzed whether the degree of expression of Twist in the renal interstitium was correlated with renal survival.
Results: Activated Twist was strongly expressed in tubular epithelial cell nuclei from the kidneys of patients with chronic kidney diseases, while little positive staining for Twist was found in the renal tubules of normal kidneys (p = 0.001). Twist protein in the tubulointerstitium was inversely correlated with estimated glomerular filtration rate (eGFR; r = -0.468, p = 0.029) and positively correlated with serum creatinine (r = 0.44, p = 0.045) and the percentage of tubulointerstitial fibrosis (r = 0.551, p = 0.000). Moreover, a high level of Twist was correlated with activation of HIF-1α expression and E-cadherin repression across all disease groups (p = 0.000, p = 0.000, respectively). By multivariate analysis, the experimental data show that the factors influencing renal survival were eGFR [relative risk (RR) 4.39 (95%CI 1.342, 14.393), p = 0.014] and the degree of expression of Twist [RR 3.43 (95% CI 1.098, 10.684), p = 0.034].
Conclusions: Our results raise the possibility that Twist activation is a common mechanism in the pathophysiology of a wide range of chronic hypoxic renal diseases and that Twist staining in renal biopsy specimens might provide a valuable histologic index of progression.
Copyright © 2012 S. Karger AG, Basel.