Ketogenic Diet May Improve GFR in People with PKD 

A new clinical study released this month demonstrated increased glomerular filtration rate (eGFR), a key indicator of kidney function, in people with polycystic kidney disease (PKD). The randomized controlled trial was published in Cell Reports Medicine and titled "Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD—a randomized controlled trial." Let’s investigate the results and discuss the important takeaways for people with PKD.

The KETO-ADPKD Trial  

The KETO-ADPKD trial is a beacon of hope for those living with this challenging condition. It tests the feasibility and impact of ketogenic diets in people with the most common hereditary form of PKD. The study divided 66 participants into three groups: a low-carbohydrate/high-fat ketogenic diet group, a water fasting group, and a control group receiving routine dietary counseling. The remarkable aspect of this trial is its human-centered approach, moving beyond the limitations of animal models to provide real-world insights.

Key Findings of the Study  

• Kidney Function: Perhaps the most promising result was the observed increase in estimated Glomerular Filtration Rate (eGFR) in the ketogenic diet group. In contrast, the control and water fasting groups experienced a decline. Improved eGFR indicates better kidney function, a critical marker for patients with PKD.
• Kidney and Liver Volume: The study reported a decrease in height-adjusted total kidney volume (htTKV) and liver volume (htTLV) in the ketogenic diet group. A reduction in total kidney volume was unexpected even though it did not reach statistical significance, which may be due to the relatively slow kidney growth typically observed.  Overall, this suggests a potential for ketogenic diets to slow ADPKD progression.
• Body Weight and Composition: The ketogenic diet group showed a notable reduction in body weight and fat mass compared to the control and water fasting groups. This finding is particularly significant as it demonstrates the diet's effectiveness in altering body composition, a crucial factor in managing ADPKD. 
• Patient Characteristics and Intervention: Participants were carefully categorized into groups that followed either a specific dietary regimen (ketogenic diet or water fasting) or received standard dietary advice for ADPKD patients.
• Duration and Participation: The trial spanned three months, with a high rate of participation and adherence to the prescribed diets, highlighting the practicality of these interventions in real-life scenarios.

Understanding ADPKD

Autosomal Dominant PKD (ADPKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys. This condition is the most prevalent kidney disease resulting from a single gene mutation, and it can lead to kidney failure. Before delving into the study, it's essential to understand that PKD affects more than just the kidneys; it often comes with a slew of systemic issues, including liver disease and cardiovascular complications. Unfortunately, treatment options for PKD are limited.

Empowering Patients with PKD

The KETO-ADPKD trial is more than a scientific study; it's a ray of hope for many who have been navigating the challenging waters of PKD. The ketogenic diet, often associated with weight loss and diabetes management, is now emerging as a potential ally in the fight against kidney diseases. They not only offer a new avenue for managing the condition but also empower patients with more control over their health through dietary choices. However, it's crucial to remember that every individual is unique, and dietary interventions should be tailored to each person's specific health needs and conditions.

Safety Considerations

When considering any new intervention, safety is paramount. The KETO-ADPKD trial meticulously analyzed safety-relevant laboratory events and other related occurrences. Notably, there were cases of increased uric acid and cholesterol levels, alongside symptoms typically associated with the initiation of a ketogenic diet, commonly referred to as "ketogenic flu." These symptoms can include headache, fatigue, and nausea, but they are generally transient and self-resolving. The authors note that long-term research on ketogenic diets for patients with type 2 diabetes and children with epilepsy show an initial increase in cholesterol followed by a return to normal or improvement in overall levels, an area that requires further study in people with PKD on a ketogenic diet. 

A particularly encouraging aspect of the trial was the high Patient-Reported Outcomes (PRO) questionnaire rating for the ketogenic diet arm. This suggests that participants found the diet not just bearable, but positively beneficial on their quality of life.The study set a high beta-hydroxybutyrate (BHB) threshold for its feasibility requirement that was not met by all participants at every check-in, yet nearly all regularly showed increased BHB levels throughout the study period, indicating consistent adherence to the dietary protocol.

Important Implications 

The KETO-ADPKD trial's findings have significant implications for the management of PKD, particularly in the context of existing treatment options and the potential long-term effects of ketogenic diets:

• Feasibility and Impact: The trial demonstrated not just the feasibility of ketogenic diets in a controlled setting, but also their potential impact on key health markers such as kidney and liver volumes and eGFR. This is encouraging news for people with PKD because it shows that it is realistic for for them to adopt a low-carbohydrate, high-fat diet as a non-drug method to help manage their condition. 
• Uric Acid Levels and Kidney Stone Risk: One observation from the trial was an increase in uric acid levels. Previous research has indicated a possible link between ketogenic diets and an elevated risk of kidney stones, particularly in epilepsy patients. However, the ketogenic diet regimen in this study was not protein- or meat-rich, which could mitigate this risk. It's a reminder that while ketogenic diets show promise, they must be carefully tailored and monitored, especially in vulnerable populations. It is important to consider that other dietary components such as oxalates contribute to overall risk of stone formation.
• Long-term Effects and Comparative Benefits: The KETO-ADPKD trial opens the door to a new avenue in ADPKD management, one that could potentially be used alongside or in place of existing therapies. It's a step towards more personalized medicine, where dietary interventions are tailored to individual patient needs and monitored for efficacy and safety over the long term.

Final Thoughts

The KETO-ADPKD study is a landmark in the field of nephrology and nutrition, demonstrating improved kidney function as shown by statistically significant increases in eGFR in people with PKD adopting a ketogenic diet. This research helps to bridge the gap between animal research on PKD and its real world applications, offering hope and a new potential pathway for managing the condition. It highlights the importance of dietary interventions in chronic disease management and underscores the need for ongoing research to fully understand the long-term effects and optimal application of these strategies.

Disclosure

Professor Dr. Roman-Ulrich Müller, the Deputy Director of Internal Medicine (Nephrology) at the University Hospital Cologne, Germany, and his team manage one of the largest ADPKD patient cohorts in Europe. He is also a member of of the Santa Barbara Nutrients Advisory Board and the primary author of this new study.

Scientific review by Jacob Kingaard, MS (Human Nutrition)  Director of Manufacturing and Product Development at SBN