Abstract
BackgroundThe kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension.MethodsWe used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney.ResultsDS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased.ConclusionsDS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.
Highlights
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people worldwide
We examined the expression level of some genes related to mitochondrial function, glycolysis, and fatty acid metabolism at 11 and 21 weeks of age
We demonstrated that the metabolites levels in the first half of the tricarboxylic acid (TCA) cycle increased; the level of succinate in the latter half of the TCA cycle decreased in Dahl salt-sensitive (DS) rats in chronic kidney disease (CKD) with cardiorenal syndrome (CRS), and the gene expression related to energy metabolism significantly changed
Summary
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people worldwide. Patients with CKD have a ten-fold increase in incidence of cardiovascular death due to common underlying causes of cardiovascular diseases (Hillege et al, 2000; Lozano et al, 2012; Smith et al, 2006), and impaired renal function is an independent risk factor for morbidity and mortality in patients with heart failure (HF). How to cite this article Tanada et al (2017), The metabolic profile of a rat model of chronic kidney disease. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury
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