Document Detail

Acid retention during kidney failure induces endothelin and aldosterone production which lead to progressive GFR decline, a situation ameliorated by alkali diet.
MedLine Citation:
PMID:  20861823     Owner:  NLM     Status:  MEDLINE    
Rats with 5/6 nephrectomy have metabolic acidosis with a progressive decline in the glomerular filtration rate (GFR) ameliorated by endothelin and aldosterone antagonists and by dietary alkali. Interestingly, rats with 2/3 nephrectomy have no metabolic acidosis yet have a progressive GFR decline induced by acid retention and ameliorated by dietary alkali. Because patients without metabolic acidosis but with a moderately reduced GFR have a progressive GFR decline, ameliorated by oral sodium bicarbonate, we used rats with 2/3 nephrectomy to model these patients. Kidney acid content, endothelin-1, and aldosterone (measured by microdialysis) were higher in the rats with 2/3 nephrectomy than those with a sham operation despite no differences in plasma acid-base parameters. The GFR of the former but not the latter was lower at 25 than at 1 week after nephrectomy. Endothelin and aldosterone antagonism improved the preservation of GFR; however, this remained lower at week 24 than at week 1. By contrast, the GFR at weeks 24 and 1 was not different if the rats were given dietary alkali to normalize the kidney acid content. Antagonist of endothelin and aldosterone yielded no added GFR benefit. Thus, our study shows that (1) the decline in GFR in 2/3 nephrectomy is mediated by acid retention-induced kidney endothelin and aldosterone production; (2) receptor antagonism and dietary alkali are not additive; and (3) dietary alkali better preserves GFR than both endothelin and aldosterone receptor antagonism.
Donald E Wesson; Jan Simoni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-22
Journal Detail:
Title:  Kidney international     Volume:  78     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-15     Completed Date:  2011-02-25     Revised Date:  2013-11-25    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1128-35     Citation Subset:  IM    
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MeSH Terms
Acid-Base Equilibrium / drug effects
Acidosis / metabolism,  physiopathology,  prevention & control*
Administration, Oral
Aldosterone / blood*
Bicarbonates / administration & dosage*
Calcium Gluconate / pharmacology
Dietary Supplements*
Disease Models, Animal
Endothelin-1 / blood*
Glomerular Filtration Rate / drug effects*
Kidney / drug effects*,  metabolism,  physiopathology
Mineralocorticoid Receptor Antagonists / pharmacology
Phenylpropionates / pharmacology
Pyrimidines / pharmacology
Rats, Wistar
Receptor, Endothelin A / antagonists & inhibitors,  metabolism
Renal Insufficiency / drug therapy*,  metabolism,  physiopathology
Spironolactone / analogs & derivatives,  pharmacology
Time Factors
Reg. No./Substance:
0/Bicarbonates; 0/Endothelin-1; 0/LU 135252; 0/Mineralocorticoid Receptor Antagonists; 0/Phenylpropionates; 0/Pyrimidines; 0/Receptor, Endothelin A; 27O7W4T232/Spironolactone; 4964P6T9RB/Aldosterone; 6995V82D0B/eplerenone; 7PRA4BLM2L/calcium bicarbonate; SQE6VB453K/Calcium Gluconate
Comment In:
Kidney Int. 2010 Dec;78(11):1065-7   [PMID:  21076447 ]

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