Ketone bodies - metabolic insights in ADPKD
Ketone bodies - metabolic insights in ADPKD
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, in which cysts gradually grow in the kidneys leading to a decline in kidney function over time. Eventually, most patients need kidney replacement therapy such as dialysis or kidney transplantation. Recent research suggests that altered energy metabolism in cystic cells may play an important role in this process and may provide new treatment possibilities.
In this thesis of Martine Knol ketone bodies were studied, an alternative energy source produced during fasting or a ketogenic diet. We found that patients with ADPKD who had higher levels of the ketone body beta-hydroxybutyrate (BHB) were associated to have a slower decline in kidney function. Nevertheless, the hormone glucagon, which stimulates BHB production, was not associated with disease progression. Probably due to complex interplay with other hormones of the glucose metabolism.
We also explored which factors influence ketone body levels in the general population. These levels were associated with age, sex, hormonal status, and lifestyle factors. Potentially modifiable factors include alcohol consumption, protein intake, and the use of oral contraceptives. Importantly, we found sex differences in the determinants of BHB concentrations. For future trials this could be used to stratify patients.
Additionally, we examined how a ketogenic diet affects metabolism in both humans and an experimental animal model. This study showed that such a diet can alter several metabolic pathways and possibly contribute to slowing down disease progression.
Together, these findings suggest that ketone bodies may play a role in slowing disease progression and could be of interest as a future treatment strategy for patients with ADPKD.