Renal expression of hypoxia inducible factor-1α in patients with chronic kidney disease: a clinicopathologic study from nephrectomized kidneys

BACKGROUND & OBJECTIVES Hypoxia inducible factor-1α (HIF-1α) has been shown to play a role in the pathogenesis of renal interstitial fibrosis. However, the relationship of HIF-1α expression intensity in human renal tissue with the degree of renal function or renal fibrosis has not been investigated. We therefore, undertook this study to assess the relationship between HIF-1α expression and degree of renal impairment and renal fibrosis using renal tissue from nephrectomized kidneys from patients with chronic kidney disease. METHODS This retrospective study was performed with 70 patients undergoing unilateral or bilateral nephrectomy because of renal cell carcinoma, urothelial cell carcinoma, or renal abscess. Immunohistochemical analysis of HIF-1α expression in non-tumourous or non-abscess renal parenchyma was performed. The patients were divided into two groups: group 1 (n=37) with low intensity HIF-1α expression and group 2 (n=33) with high intensity HIF-1α expression. RESULTS The intensity of renal HIF-1α expression was significantly associated with serum creatinine level (P =0.005), estimated glomerular filtration rate (P=0.02), fibrosis score of the interstitium (P=0.004) and glomerular sclerosis (P=0.013). A high intensity of HIF-1α expression tended to be associated with lower serum creatinine, higher estimated glomerular filtration rate, low interstitial fibrosis score and low glomerular sclerosis. In addition, multivariate analysis by step-wise logistic regression demonstrated that interstitial fibrosis was the only independent factor associated with the intensity of renal HIF-1α expression (OR 4.107, CI 1.535-11.313, P=0.005). INTERPRETATION & CONCLUSIONS This study demonstrated a correlation between intensity of HIF-1α expression and degree of renal interstitial fibrosis. The association demonstrated an elevated HIF-1α expression in less severe kidney disease. The intensity of HIF-1α renal expression plays a role in the pathogenesis of chronic kidney disease.