The Metabolic Profile of a Rat Model of Chronic Kidney Disease

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2017 Jun 1

PMID 28560105

Citations 12

Authors

Yohei Tanada

Junji Okuda

Takao Kato

Eri Minamino-Muta

Ichijiro Murata

Tomoyoshi Soga

Tetsuo Shioi

Takeshi Kimura

Affiliations

Soon will be listed here.

Abstract

Background: The 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.

Methods: We 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.

Results: DS 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.

Conclusions: DS 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.

Citing Articles

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats.

Jiang Q, Yang Q, Zhang C, Hou C, Hong W, Du M Respir Res. 2024; 25(1):288.

PMID: 39080603 PMC: 11290206. DOI: 10.1186/s12931-024-02916-w.

DNA methylation of miR-181a-5p mediated by DNMT3b drives renal interstitial fibrosis developed from acute kidney injury.

Liu H, Deng Y, Luo G, Yang Y, Xie B, Diao H Epigenomics. 2024; 16(13):945-960.

PMID: 39023272 PMC: 11370974. DOI: 10.1080/17501911.2024.2370229.

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats.

He L, Zuo Q, Ma S, Zhang G, Wang Z, Zhang T Ren Fail. 2024; 46(1):2300314.

PMID: 38189082 PMC: 10776083. DOI: 10.1080/0886022X.2023.2300314.

Effects of Exercise Training on Mitochondrial Fatty Acid β-Oxidation in the Kidneys of Dahl Salt-Sensitive Rats.

Namai-Takahashi A, Takahashi J, Ogawa Y, Sakuyama A, Xu L, Miura T Int J Mol Sci. 2023; 24(21).

PMID: 37958585 PMC: 10649976. DOI: 10.3390/ijms242115601.

Metabolic Responses of Normal Rat Kidneys to a High Salt Intake.

Shimada S, Hoffmann B, Yang C, Kurth T, Greene A, Liang M Function (Oxf). 2023; 4(5):zqad031.

PMID: 37575482 PMC: 10413938. DOI: 10.1093/function/zqad031.

References

Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M, Nishioka T . Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J Proteome Res. 2003; 2(5):488-94. DOI: 10.1021/pr034020m. View

van Timmeren M, Bakker S, Vaidya V, Bailly V, Schuurs T, Damman J . Tubular kidney injury molecule-1 in protein-overload nephropathy. Am J Physiol Renal Physiol. 2006; 291(2):F456-64. DOI: 10.1152/ajprenal.00403.2005. View

Bidani A, Griffin K . Pathophysiology of hypertensive renal damage: implications for therapy. Hypertension. 2004; 44(5):595-601. DOI: 10.1161/01.HYP.0000145180.38707.84. View

Che R, Yuan Y, Huang S, Zhang A . Mitochondrial dysfunction in the pathophysiology of renal diseases. Am J Physiol Renal Physiol. 2013; 306(4):F367-78. DOI: 10.1152/ajprenal.00571.2013. View

Morooka H, Iwanaga Y, Tamaki Y, Takase T, Akahoshi Y, Nakano Y . Chronic administration of oral vasopressin type 2 receptor antagonist tolvaptan exerts both myocardial and renal protective effects in rats with hypertensive heart failure. Circ Heart Fail. 2012; 5(4):484-92. DOI: 10.1161/CIRCHEARTFAILURE.111.965392. View

Lekgabe E, Kiriazis H, Zhao C, Xu Q, Moore X, Su Y . Relaxin reverses cardiac and renal fibrosis in spontaneously hypertensive rats. Hypertension. 2005; 46(2):412-8. DOI: 10.1161/01.HYP.0000171930.00697.2f. View

Stein L, Imai S . The dynamic regulation of NAD metabolism in mitochondria. Trends Endocrinol Metab. 2012; 23(9):420-8. PMC: 3683958. DOI: 10.1016/j.tem.2012.06.005. View

Du J, Fan Y, Hitomi H, Kiyomoto H, Kimura S, Kong C . Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats. Am J Physiol Renal Physiol. 2009; 297(3):F802-8. DOI: 10.1152/ajprenal.00197.2009. View

Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A . NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000; 24(4):349-54. DOI: 10.1038/74166. View

10.

RAPP J, Dene H . Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 1985; 7(3 Pt 1):340-9. View

11.

Tran M, Tam D, Bardia A, Bhasin M, Rowe G, Kher A . PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice. J Clin Invest. 2011; 121(10):4003-14. PMC: 3195479. DOI: 10.1172/JCI58662. View

12.

Zaza G, Granata S, Masola V, Rugiu C, Fantin F, Gesualdo L . Downregulation of nuclear-encoded genes of oxidative metabolism in dialyzed chronic kidney disease patients. PLoS One. 2013; 8(10):e77847. PMC: 3810143. DOI: 10.1371/journal.pone.0077847. View

13.

Inoko M, Kihara Y, Morii I, Fujiwara H, Sasayama S . Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats. Am J Physiol. 1994; 267(6 Pt 2):H2471-82. DOI: 10.1152/ajpheart.1994.267.6.H2471. View

14.

Sharma K, Karl B, Mathew A, Gangoiti J, Wassel C, Saito R . Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J Am Soc Nephrol. 2013; 24(11):1901-12. PMC: 3810086. DOI: 10.1681/ASN.2013020126. View

15.

Zhu S, Yang Y, Hu J, Qian L, Jiang Y, Li X . Wld(S) ameliorates renal injury in a type 1 diabetic mouse model. Am J Physiol Renal Physiol. 2014; 306(11):F1348-56. DOI: 10.1152/ajprenal.00418.2013. View

16.

Rubattu S, Mennuni S, Testa M, Mennuni M, Pierelli G, Pagliaro B . Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress?. Int J Mol Sci. 2013; 14(11):23011-32. PMC: 3856103. DOI: 10.3390/ijms141123011. View

17.

Niizuma S, Inuzuka Y, Okuda J, Kato T, Kawashima T, Tamaki Y . Effect of persistent activation of phosphoinositide 3-kinase on heart. Life Sci. 2012; 90(15-16):619-28. DOI: 10.1016/j.lfs.2012.02.010. View

18.

Tanada Y, Shioi T, Kato T, Kawamoto A, Okuda J, Kimura T . Branched-chain amino acids ameliorate heart failure with cardiac cachexia in rats. Life Sci. 2015; 137:20-7. DOI: 10.1016/j.lfs.2015.06.021. View

19.

Zheleznova N, Yang C, Ryan R, Halligan B, Liang M, Greene A . Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat. Physiol Genomics. 2012; 44(17):829-42. PMC: 3472460. DOI: 10.1152/physiolgenomics.00060.2012. View

20.

Wang L, Lee J, Kwak J, He Y, Kim S, Choi M . Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2007; 294(3):F508-17. DOI: 10.1152/ajprenal.00306.2007. View