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Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence
Carla Pezzuoli1,2, Giuseppe Biagini3, Riccardo Magistroni2,4
1Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Abstract:
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and enlargement of multiple kidney cysts, leading to progressive kidney function decline. To date, Tolvaptan, the only approved treatment for this condition, is able to slow down the loss of annual kidney function without stopping the progression of the disease. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the drug's impact on quality of life. The recent literature suggests that cystic cells are subject to several metabolic dysregulations, particularly in the glucose pathway, and mitochondrial abnormalities, leading to decreased oxidative phosphorylation and impaired fatty acid oxidation. This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions' effect.
Insights
Ketosis, through various dietary strategies, shows promise for managing Autosomal Dominant Polycystic Kidney Disease (ADPKD). This approach may offer an alternative or complementary therapy to current treatments, potentially improving patient outcomes.
Area of Science:
- Nephrology
- Metabolic Disorders
- Genetics
Background:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder causing kidney cyst development and progressive function loss.
- Current treatment, Tolvaptan, slows but does not halt disease progression and has compliance issues due to side effects.
- Metabolic dysregulations, including glucose pathway and mitochondrial abnormalities, are implicated in ADPKD pathogenesis.
Purpose of the Study:
- To review the potential of ketosis as a therapeutic strategy for ADPKD.
- To explore various ketogenic dietary interventions for ADPKD management.
- To investigate the role of gut microbiota in ketogenic intervention efficacy for ADPKD.
Main Methods:
- Literature review of studies on ketogenic interventions and ADPKD.
- Analysis of metabolic pathways, including glucose metabolism and mitochondrial function in ADPKD.
- Examination of research on dietary interventions: calorie restriction, intermittent fasting, time-restricted feeding, ketogenic diets, and exogenous ketosis.
Main Results:
- Cystic cells in ADPKD exhibit metabolic dysregulation, particularly in glucose metabolism and mitochondrial function.
- Ketogenic dietary interventions show potential for managing ADPKD by targeting these metabolic abnormalities.
- The gut microbiota may play a role in mediating the effects of ketogenic interventions in ADPKD.
Conclusions:
- Ketosis, via ketogenic dietary interventions, represents a promising therapeutic avenue for ADPKD.
- Further research is warranted to elucidate the mechanisms and optimize ketogenic strategies for ADPKD patients.
- Investigating the interplay between microbiota and ketogenic interventions could lead to novel therapeutic approaches for ADPKD.
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