Acute Kidney Injury Markers and 24-Hour Blood Pressure after Short-Term High Salt and Ketone Supplementation in Apparently Healthy Adults

Background: Short-term high salt intake may increase acute kidney injury (AKI) biomarkers, which are indicative of kidney damage. Both high salt and kidney injury are associated with increased kidney disease risk and poorer long-term blood pressure (BP) control. Rodent studies demonstrate increasing ketones mitigates the effect of high salt on kidney injury and BP. However, whether ketone supplementation protects against the adverse effects of high salt has not been translated to humans. Therefore, we examined AKI biomarkers and 24-hour ambulatory BP after short-term high salt and ketone supplementation in generally healthy adults. Methods: Eleven participants (9 M/2 F, age 32 ± 12 years, body mass index: 25 ± 3 kg/m 2 ; mean ± SD) were included in this randomized, crossover study.Participants completed three 10-day conditions: A) placebo capsules and placebo drink; B) salt capsules and placebo drink; and C) salt capsules and ketone drink. Participants were counseled to adhere to a low-salt diet (0.8 mg of sodium/kcal/day) during the interventions. For high salt loading, we provided salt capsules to increase total sodium consumption to ~2 mg/kcal/day. Participants consumed 12 g of ketone supplement drink 3x/day (36 g total/day) on the ketone condition. For the placebo drink, participants consumed equivalent volume of a taste-matched ketone-depleted drink. 24-hour urine samples were collected to assess AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and the product of [TIMP-2 ● IGFBP7] all indexed to urine flow rate. We also measured serum creatinine as a proxy for glomerular filtration rate. For ambulatory BP, participants wore a BP monitor programmed to measure brachial BP every 20 minutes during awake hours and every 30 minutes during sleep. We calculated BP dipping as the percentage drop in BP from awake to sleep as: % dip = [(awake BP - sleep BP) / awake BP] x 100. Depending on data normality, repeated measures ANOVA or Friedman test and Pearson’s r or Spearmen’s ρ correlations were run with α set at ≤ 0.05. Results: There were no changes across conditions for AKI biomarkers including NGAL (placebo: 8.1 ± 18.0 vs. salt: 5.8 ± 9.5 vs. ketone: 5.9 ± 11.4 ng/min, p =0.96), KIM-1 ( p >0.99), TIMP-2 ( p =0.97), IGFBP7 ( p >0.99), and [TIMP-2 ● IGFBP7] ( p >0.99). Serum creatinine also did not differ across conditions ( p >0.99). Ambulatory BP dipping did not differ across conditions for systolic BP (placebo: 15 ± 7% vs. salt: 9 ± 12% vs. ketone: 10 ± 11%, p =0.58), nor diastolic BP ( p =0.90). Interestingly, when data were pooled across all conditions, serum creatinine was inversely correlated with systolic BP dipping (ρ=-0.40, p =0.04) but not diastolic BP dipping ( r =0.34, p =0.08). Conclusion: Our preliminary data indicate there was no effect of high salt or ketone supplementation on urinary AKI biomarkers or ambulatory BP. Nonetheless, even in apparently healthy adults, higher serum creatinine was correlated with lower systolic BP dipping, irrespective of sodium intake or ketone supplementation. Funding: This research is supported by NIH grants K01HL147998, AHA 24PRE1201426, and UL1TR003106. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.