Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.
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Double immunofluorescence staining for mindin (red) and CD68 (green) in atherosclerotic plaques of HFD-treated APOE-/- mice. In Issue 11 of Clinical Science, Zhu et al. discuss mindin deficiency as a novel mediator in protecting against foam cell formation and atherosclerosis, through direct interaction with LXR-β; for details, see pages 1199–1213.
Research Article|
June 15 2018
Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats
Sarah C. Ray;
Sarah C. Ray
1Department of Physiology, Medical College of Georgia, Augusta University
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Bansari Patel;
Bansari Patel
1Department of Physiology, Medical College of Georgia, Augusta University
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Debra L. Irsik;
Debra L. Irsik
1Department of Physiology, Medical College of Georgia, Augusta University
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Jingping Sun;
Jingping Sun
1Department of Physiology, Medical College of Georgia, Augusta University
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Hiram Ocasio;
Hiram Ocasio
1Department of Physiology, Medical College of Georgia, Augusta University
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Gene R. Crislip;
Gene R. Crislip
1Department of Physiology, Medical College of Georgia, Augusta University
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Chunhua H. Jin;
Chunhua H. Jin
2Department of Medicine, Division of Nephrology, University of Alabama Birmingham, Alabama, USA
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JianKang Chen;
JianKang Chen
3Department of Cell Biology and Anatomy, Augusta University, Augusta, Georgia, USA
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Babak Baban;
Babak Baban
4Department of Oral Biology, Augusta University, Augusta, Georgia, USA
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Aaron J. Polichnowski;
Aaron J. Polichnowski
5Department of Biological Sciences, East Tennessee State University, Johnson City, Tennessee, USA
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Paul M. O’Connor
1Department of Physiology, Medical College of Georgia, Augusta University
Correspondence: Paul M O’Connor ([email protected])
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Publisher: Portland Press Ltd
Received:
December 14 2017
Revision Received:
April 10 2018
Accepted:
April 12 2018
Accepted Manuscript online:
April 12 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (11): 1179–1197.
Article history
Received:
December 14 2017
Revision Received:
April 10 2018
Accepted:
April 12 2018
Accepted Manuscript online:
April 12 2018
Connected Content
A commentary has been published:
Buffering chronic kidney disease with sodium bicarbonate
Citation
Sarah C. Ray, Bansari Patel, Debra L. Irsik, Jingping Sun, Hiram Ocasio, Gene R. Crislip, Chunhua H. Jin, JianKang Chen, Babak Baban, Aaron J. Polichnowski, Paul M. O’Connor; Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats. Clin Sci (Lond) 14 June 2018; 132 (11): 1179–1197. doi: https://doi.org/10.1042/CS20171630
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