Journal
NEPHRON EXPERIMENTAL NEPHROLOGY
Volume 98, Issue 1, Pages E8-E12Publisher
KARGER
DOI: 10.1159/000079927
Keywords
kidney failure; anoxia; hypoxia; ischemia; tubules; hypoxia-inducible factor; hypoxia-responsive element; vascular endothelial growth factor; renin angiotensin system; fibrosis
Categories
Ask authors/readers for more resources
Many clinical observations suggest common mediators in the progression of kidney disease leading to eventual kidney failure. Among them, accumulating evidence emphasizes the role of chronic hypoxia in the tubulointerstitium in this role. When advanced, tubulointerstitial damage is associated with the loss of peritubular capillaries, impairing blood delivery. Associated interstitial fibrosis further impairs oxygen diffusion and supply to tubular and interstitial cells. This in turn exacerbates chronic hypoxia in this compartment, resulting in a vicious cycle. Both singly or together, glomerular injury and vasoconstriction of efferent arterioles due to an imbalance in vasoactive substances decrease post-glomerular peritubular capillary blood flow and contribute to chronic hypoxia in the tubulointerstitium. Anemia in kidney disease also plays a significant role in hypoxia of the kidney. Moreover, increased metabolic demand in tubular cells, as observed in glomerular hyperfiltration for example, can cause relative hypoxia. Importantly, these factors can affect the kidney before the appearance of significant pathological changes in the vasculature and predispose it to tubulointerstitial injury. Therapeutic approaches targeting chronic hypoxia in the kidney should be effective against a broad range of renal diseases. Recent studies have elucidated the mechanisms of hypoxia-induced transcription, giving hope for the development of novel therapeutic approaches against this final common pathway. Copyright (C) 2004 S. Karger AG, Basel.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available