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1,3-Butanediol attenuates hypertension and suppresses kidney injury in female rats.

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 β-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 females or the absence of high salt has not been investigated. This study tests the hypothesis that 1,3-Butanediol attenuates hypertension and progression of CKD in female S-SHR(11). S-SHR(11) 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 weeks and were maintained on a 0.3% NaCl rodent diet (n=12-14/group). Blood pressure was measured after 6 and 9 weeks of treatment by tail-cuff plethysmography, and after 10 weeks urine and tissues were collected. Activity of the treatment was confirmed by measuring plasma β-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 weeks of treatment compared to control . The treated group had significantly smaller spleens and increased renal anti-inflammatory molecules interleukin-10 and granulocyte-macrophage colony-stimulating factor suggesting reduced inflammation. The current data demonstrate that 1,3-Butanediol lowers blood pressure and renal injury in females and could be a novel nutritional intervention for the treatment of CKD.