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Renal tubulointerstitial hypoxia: Cause and consequence of kidney dysfunction
Uppsala universitet, Integrativ Fysiologi.
Uppsala universitet, Integrativ Fysiologi.
2011 (English)In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 38, no 7, 424-430 p.Article in journal (Refereed) Published
Abstract [en]

1. Intrarenal oxygen availability is the balance between supply, mainly dependent on renal blood flow, and demand, determined by the basal metabolic demand and the energy-requiring tubular electrolyte transport. Renal blood flow is maintained within close limits in order to sustain stable glomerular filtration, so increased intrarenal oxygen consumption is likely to cause tissue hypoxia.

2. The increased oxygen consumption is closely linked to increased oxidative stress, which increases mitochondrial oxygen usage and reduces tubular electrolyte transport efficiency, with both contributing to increased total oxygen consumption.

3. Tubulointerstitial hypoxia stimulates the production of collagen I and alpha-smooth muscle actin, indicators of increased fibrogenesis. Furthermore, the hypoxic environment induces epithelial-mesenchymal transdifferentiation and aggravates fibrosis, which results in reduced peritubular blood perfusion and oxygen delivery due to capillary rarefaction.

4. Increased oxygen consumption, capillary rarefaction and increased diffusion distance due to the increased fibrosis per se further aggravate the interstitial hypoxia.

5. Recently, it has been demonstrated that hypoxia simulates the infiltration and maturation of immune cells, which provides an explanation for the general inflammation commonly associated with the progression of chronic kidney disease. 6. Therapies targeting interstitial hypoxia could potentially reduce the progression of chronic renal failure in millions of patients who are otherwise likely to eventually present with fully developed end-stage renal disease.

Place, publisher, year, edition, pages
2011. Vol. 38, no 7, 424-430 p.
Keyword [en]
fibrosis, oxidative stress, oxygen consumption, tubulointerstitial hypoxia
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-99328DOI: 10.1111/j.1440-1681.2011.05532.xISI: 000292100300012PubMedID: 21545630OAI: diva2:657143
Available from: 2011-07-11 Created: 2013-10-15 Last updated: 2013-10-18

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