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Updated: Jul 11, 2025
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Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
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Higher beta-hydroxybutyrate ketone levels associated with a slower kidney function decline in ADPKD
Martine G E Knol1, Thomas Bais1, Paul Geertsema1
1Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Summary
Higher beta-hydroxybutyrate (BHB) levels are linked to slower kidney function decline in autosomal dominant polycystic kidney disease (ADPKD). This suggests that increasing BHB may be a therapeutic strategy for ADPKD patients.
Area of Science:
- Nephrology
- Metabolic Disorders
- Biochemistry
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is characterized by dysregulated cellular energy metabolism, with a reliance on glucose and impaired ketone body utilization.
- Animal models suggest that elevated ketone body concentrations can mitigate polycystic kidney disease progression.
Purpose of the Study:
- To investigate the association between endogenous plasma beta-hydroxybutyrate (BHB) concentrations and disease progression in patients with ADPKD.
Main Methods:
- Analysis of data from 521 patients with ADPKD from the multi-center prospective observational DIPAK cohort study.
- Baseline plasma BHB levels were measured using nuclear magnetic resonance spectroscopy.
- Linear regression and linear mixed-effects modeling were employed to assess cross-sectional and longitudinal associations, respectively.
Main Results:
- The median BHB concentration was 94 µmol/L. No cross-sectional association was found between BHB and estimated glomerular filtration rate (eGFR) or height-adjusted total kidney volume (htTKV).
- Longitudinally, BHB was positively associated with the eGFR slope (B = 0.35 mL/min/1.73 m2, P = .007), indicating a slower decline in kidney function.
- Each doubling in BHB concentration was associated with an improvement in the annual eGFR rate by 0.33 mL/min/1.73 m2 (95% CI 0.09 to 0.57, P = .008) after confounder adjustment.
Conclusions:
- These observational findings support the hypothesis that higher BHB concentrations are associated with reduced kidney function decline in ADPKD.
- Interventions aimed at increasing BHB levels may represent a potential therapeutic strategy for slowing disease progression in ADPKD.
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