Ketogenic dietary interventions in autosomal dominant polycystic kidney disease-a retrospective case series study: first insights into feasibility, safety and effects

Abstract

Background: Our laboratory published the first evidence that nutritional ketosis, induced by a ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in polycystic kidney disease (PKD) animal models. We reasoned that, due to their frequent use for numerous health benefits, some autosomal dominant PKD (ADPKD) patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect the first real-life observations of ADPKD patients about safety, feasibility and possible benefits of KDIs in ADPKD as part of a translational project pipeline.

Methods: Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects and the feasibility and safety of KDIs in questionnaire-based interviews.

Results: A total of 131 ADPKD patients took part in this study. About 74 executed a KD and 52 a TRD for 6 months on average. A total of 86% of participants reported that KDIs had improved their overall health, 67% described improvements in ADPKD-associated health issues, 90% observed significant weight loss, 64% of participants with hypertension reported improvements in blood pressure, 66% noticed adverse effects that are frequently observed with KDIs, 22 participants reported safety concerns like hyperlipidemia, 45 participants reported slight improvements in estimated glomerular filtration rate and 92% experienced KDIs as feasible while 53% reported breaks during their diet.

Conclusions: Our preliminary data indicate that KDIs may be safe, feasible and potentially beneficial for ADPKD patients, highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.

Keywords: autosomal dominant polycystic kidney disease; caloric restriction; intermittent fasting; ketogenic diet.

FIGURE 1:

The study cohort KDIs. (A) Flow diagram of the case series study cohort KDIs. PKD patients were recruited by the Weimbs Laboratory and the University Hospital of Cologne to participate in questionnaire-based interviews about the experience of PKD patients with KDIs. (B) Description of the study cohort: distribution of age, sex and type of KDIs. (C) Average time on KDIs. Time on the diet is displayed as the median average. (D) Controlling measures of participants on a KD. Participants were asked how they control to reach ketosis. (E) Self-reported ketone body levels of participants who measured KB in the blood or urine. KB levels are displayed as the median average. N for KB in blood = 24. N for KB in urine = 10. (F) Fasting cycles used by participants executing a TRD. Participants were asked to specify their fasting cycle when practicing a TRD. n = 48. (G) Reason for experimenting with KDIs. Participants were asked why they started a KDI. (H) Resources used for starting a KDI. Participants were asked how they found out about KDIs in PKD.

FIGURE 2:

Dietary impact on health and well-being and PKD-related HIs. (A) Impact of KDIs on personal health and well-being. Participants were asked whether their diet had an impact on their overall health and well-being. (B) Impact of KDIs on ADPKD symptoms. Participants were asked whether their diet improved personal ADPKD symptoms. (C) Presence of recurrent HIs commonly associated with PKD. Participants were asked whether they experienced any recurrent HIs related to PKD before starting their diet. (D) Specification of recurrent HIs and their improvements. Participants were asked to specify recurrent HIs before starting their diet and respective improvements after starting KDIs using a list of common PKD-associated symptoms. (E) Impact of KDIs on recurrent HIs associated with PKD. Participants were asked whether any old recurrent HIs have changed after starting their diet. Five participants reported both improvement and worsening of old recurrent HIs.

FIGURE 3:

Impact on weight. (A) Weight loss upon the start of KDIs. Participants were asked whether they experienced any weight loss after starting their diet. (B) Median average weight loss. Participants experiencing weight loss were asked for their starting weight and average weight loss. Total n = 103, KD n = 60, TRD n = 38. (C) Analysis of BMIs before and after starting KDIs of participants experiencing weight loss. n = 97. Dots are color-coded according to the BMI classifications. (D) Course of weight loss. Participants who experienced weight loss were asked whether weight loss has leveled off or was continuing over time. (E) BMI classification of participants experiencing weight loss before and after starting KDIs. n = 97. Statistical analyses by Mann–Whitney U-test. Error bars represent the median average with interquartile range.

FIGURE 4:

Impact on hypertension and water consumption. (A) Presence of arterial hypertension. Participants were asked whether they were diagnosed with hypertension or have problems with high BP. (B) Impact on BP on the start of KDIs. Participants with hypertension were asked whether they experienced any changes in BP after starting their diet. (C) Analysis of self-reported BP values from participants with hypertension before and after starting KDIs. n = 56. Error bars represent the median average with interquartile range. (D) Separate analysis for KD and TRD of self-reported BP values from participants with hypertension. KD n = 32, TRD n = 21. Box and whisker error bars represent median average with minimum to maximum. Statistical analysis by Mann–Whitney U-test. (E) Impact on water consumption. Participants were asked whether they experienced changes in water intake after starting KDIs. Since tolvaptan treatment significantly alters water consumption, participants on tolvaptan were analyzed separately. (F) Analysis of self-reported water consumption before and after starting KDIs. Since tolvaptan treatment significantly alters water consumption, participants on tolvaptan were excluded from this analysis. The cohort was analyzed separately based on whether participants reported changes or no changes in water consumption. Statistical analysis by Mann–Whitney U-test. Error bars represent the median average with interquartile range. n (experienced changes) = 57; n (no changes) = 33.

FIGURE 5:

Impact on kidney function. (A) Impact on kidney function. Participants were asked whether they experienced changes in kidney function after starting KDIs. Total n = 70. Participants with documented ketosis = 22. (B) Paired analysis of self-reported changes in eGFR before and after starting KDIs. Total n = 70, participants with documented ketosis = 22. Statistical analysis by paired t-test. Error bars represent the mean average with standard deviation. (C) Correlation analysis between eGFR difference before and after starting the diet with corresponding mean serum BHB levels reveals a positive correlation. Number of participants with both self-reported eGFR values and serum BHB levels = 14. Statistical analysis by nonparametric Spearman correlation. Line represents best fit and dotted lines represent 95% confidence intervals. P = 0.0459.

FIGURE 6:

Side effects and safety concerns. (A) New HIs on the start of KDIs. Participants were asked whether they experienced new HIs after starting their diet. (B) Specification of side effects on the start of KDIs. Participants were asked to specify those new side effects and their resolution over time using a list of common symptoms associated with KDIs. (C) Persistence of side effects. Participants were asked whether new side effects were resolving over time. (D) Safety concerns upon the start of KDIs. Participants were asked whether they or their doctors noticed changes that raised safety concerns. (E) Analysis of self-reported cholesterol levels before and after starting KDIs. Statistical analysis by Wilcoxon matched pairs signed rank test. Error bars represent the median average with interquartile range. *P < 0.05, **P < 0.01, ***P < 0.001, ****P ≤ 0.0001.

FIGURE 7:

Feasibility of KDIs and translational project pipeline. (A) Implementation of KDIs. Participants were asked how they experienced the switch from ‘standard’ nutrition to KDIs. (B) Implementation of KDIs. Participants were asked whether food preparation for KDIs takes more time than ‘standard’ food. n = 130. (C) Feasibility of KDIs. Participants were asked whether their diet is easy to do for people with ADPKD. n = 130. (D) Feasibility of KDIs. Participants were asked whether they would recommend their diet to friends or family members with ADPKD. (E) Adherence to KDIs. Participants were asked to rate the overall feasibility and adherence of their diet in daily life. (F) Adherence to KDIs. Participants were asked whether they had a break in between their diets. (G) Flow diagram showing the translational project pipeline of the University Hospital Cologne and the Weimbs Laboratory to translate KDIs into the clinical setting of ADPKD. The first results from these trials are expected in 2021 and early 2022.