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Renal Tubulointerstitial Hypoxia: Cause and Consequence of Kidney Dysunction.
MedLine Citation:
PMID:  21545630     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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; both contributing to increased total oxygen consumption. 3. Tubulointerstitial hypoxia stimulates productions of collagen I and α-smooth muscle actin, indications of increased fibrogenesis. Furthermore, the hypoxic environment induces epithelial-mesenchymal transdifferentiation and aggravating fibrosis, which result in reduced peritubular blood perfusion and oxygen delivery due to capillary rarefaction. 3. Increased oxygen consumption, capillary rarefaction and increased diffusion distance due to the increased fibrosis per se further aggravate the interstitial hypoxia. 4. Recently, it has also been demonstrated that hypoxia simulates infiltration and maturation of immune cells, which provides an explanation for the general inflammation commonly associated with the progression of chronic kidney disease. 5. Therapies targeting interstitial hypoxia could potentially reduce the progression of chronic renal failure in millions of patients that otherwise are likely to eventually present with fully developed end-stage renal disease.
Authors:
Fredrik Palm; Lina Nordquist
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-5
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden Division of Nephrology and Hypertension, Georgetown University, Washington DC, USA.
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