Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 319, Issue 1, Pages F106-F114Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00141.2020
Keywords
blood pressure; chronic kidney disease; ketogenic diet; nutritional intervention; renal injury
Categories
Funding
- National Heart, Lung, and Blood Institute [R01HL134711, R01HL137673]
- American Heart Association [20PRE35120561]
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Thirty-seven million people in the United States are estimated to have chronic kidney disease (CKD). Hypertension (HTN) is the second leading risk factor for developing kidney disease. A recent study reported that increasing levels of beta-hydroxybutyrate levels by administration of its precursor, 1,3-butanediol, decreased salt-induced HTN in male Dahl salt-sensitive (S) rats. The effect of 1,3-butanediol on hypertensive kidney disease in female rats or the absence of high salt has not been investigated. This study tested the hypothesis that 1,3-butanediol attenuates HTN and the progression of CKD in female S-SHR (11) rats. The S-SHR (11) strain is a congenic rat strain generated from genetic modification of the Dahl S rat, previously characterized as a model of accelerated renal disease. Rats received 1,3-butanediol (20% via drinking water) or control for 10 wk and were maintained on a 0.3% NaCl rodent diet (n = 12-14 rats/group). Blood pressure was measured after 6 and 9 wk of treatment by tail-cuff plethysmography; after 10 wk, urine and tissues were collected. Activity of the treatment was confirmed by measuring plasma beta-hydroxybutyrate levels, which were greater in the treated group. The 1,3-butanediol-treated group had lower systolic blood pressure, proteinuria, plasma creatinine, and renal fibrosis after 9 wk of treatment compared with controls. The treated group had significantly smaller spleens and increased the renal anti-inflammatory molecules interleukin-10 and granulocyte-macrophage colony-stimulating factor, suggesting reduced inflammation. The present data demonstrate that 1,3-butanediol lowers blood pressure and renal injury in female rats and could be a novel nutritional intervention for the treatment of CKD.
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