Increasing kidney oxygenation as a potential therapeutic avenue for kidney disease
Point of View
Increasing kidney oxygenation as a potential therapeutic avenue for kidney disease
Nikki R Adler, Department of Physiology, Monash University, PO BOx 13F, Melbourne, Victoria 3800, Melbourne, Australia. E-mail: nradl2 at student dot monash dot edu
Manuscript received 23 Jul 2009; first decision 5 Aug 2009; revised 3 Oct 2009; accepted and published 3 Oct 2009
Abstract:
It is important to investigate the mechanisms of chronic kidney disease as it is a public health problem worldwide. The unique architecture of the kidney vasculature underpins the kidney’s susceptibility to hypoxia. The countercurrent arrangement of arteries and veins in the renal cortex and of capillaries (ascending and descending) in the medulla contributes to decreased oxygen availability. Kidney disease is associated with loss of peritubular capillaries in the tubulointerstitium. Tissue hypoxia contributes to the progression and pathogenesis of chronic kidney disease. Hypoxia occurs in the tubulointerstitium prior to structural microvascular damage. Thus, hypoxia is a pathogenic factor in early stage renal disease. Approaches to increase intrarenal oxygenation form a potential therapeutic target. Presently, inhibition of the renin angiotensin system is used to treat chronic kidney disease. Angiotensin-II receptor antagonists and angiotensin-converting-enzyme inhibitors afford renoprotection in part by altering the balance between oxygen delivery and oxygen consumption, thereby treating chronic hypoxia in the tubulointerstitium. Erythropoietin (EPO) may confer renal cytoprotection and improve kidney oxygenation. However, its efficacy in the treatment of chronic renal disease in the human condition is yet to be established. Modulation of the hypoxia inducible factor (HIF) system, via prolyl hydroxylase inhibitors, is a potential therapeutic target for the treatment of chronic kidney disease. Additional research should be conducted to further elucidate the mechanisms of kidney oxygenation and the adaptive hypoxic response.
Conflict of interests: none
Some rights reserved, N.R.Adler. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by-nc-sa/3.0/
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