Short Term Induction of Ketosis in PKD
Condition: ADPKD
MeSH terms: Ketosis
Study type: Interventional

Summary: 
      Recently, it has been shown that ketose-inducing dietary interventions slow disease
      progression in animal models of polycystic kidney disease (PKD), even when the state of
      ketosis is only induced for a short period of time. The present study aims to investigate the
      effects of short term ketosis on total kidney volume (TKV) (and other parameters) in 10
      ADPKD-patients with rapidly progressive disease.
    

Detailed description: 
      Recently, dietary models inducing ketosis have been shown to inhibit disease progression in
      animal models of PKD. Those beneficial dietary models included time-restricted feeding (TRF)
      without caloric reduction, ad libitum administered ketogenic diet (KD) and acute short-term
      fasting in mouse, rat and feline models of PKD.

      In a PKD rat model, TRF without caloric reduction resulted in a strong inhibition of mTOR
      signaling, proliferation and fibrosis in the affected kidneys. The adminstration of an ad
      libitum fed KD led to similar results. In rat, mouse and feline models of PKD, acute fasting
      led to a significant reduction of cyst volume. Therefore, cystic cells seem to be
      metabolically inflexible and exhibit an altered metabolism characterized by increased
      glycolysis and, amongst others, defective fatty acid oxidation, similar to the Warburg effect
      in cancer. (Torres, Kruger et al. 2019)

      While those beneficial observations were made in mouse, rat and feline models of PKD, the
      effects of a ketogenic diet in human ADPKD patients have not been investigated yet, even
      though the adminstration of ketogenic diets is used as a treatment for epilepsy in children
      since the 1920s and fasting is one of the oldest medical procedures.

      Therefore, the aim of the present study is to investigate the effects of a short-period
      ketonic state in 10 ADPKD patients with fast progressive disease.

      10 ADPKD-patients (aged 18-60 years, CKD G 1-3a) will be enrolled after giving informed
      consent. These 10 subjects will go through four trial-related visits. During these visits,
      physical examinations will be performed, blood will be drawn, urine will be collected and
      ketone body measurements in breath, blood and urine will be carried out. Each study visit
      includes an abdominal MRI-scan. Between visit 1 and visit 2, patients will eat their regular
      carbohydrate-rich diet. After visit 2, a ketonic state will be induced in those patients.
      Patients can choose whether the ketonic state will be induced by acute fasting for 72 hours
      (under sufficient water consumption and salt substitution) or by eating a KD for 14 days.
      Study visit 3 will take place within 72 hours after finishing the dietary intervention. After
      study visit 3, patients will restart eating their regular diet. Study visit 4 will provide
      follow-up data 3-6 weeks after the dietary intervention.

      After study completion, the relative difference of TKV measured by MRI-based volumetry of the
      kidneys immediately before and immediately after the ketonic state, will be compared to TKV
      growth/decline while eating a regular carbohydrate-rich diet.

      In general, patients are counselled in our outpatient department as part of "The German
      AD(H)PKD Registry" (more than 700 patients enrolled). As from those patients, clinical data,
      laboratory data and imaging studies are present, identification and recruitment of patients
      with fast rapidly progressing disease will be facilitated. Also, the investigators are
      closely liaised with the German self-help group PKDCure (PKD Familiaere Zystennieren e.V.),
      which is dedicated to ADPKD-linked research. This will facilitate recruitment of patients
      even more.

      Data obtained from the study visits will be collected. The parameters listed below constitute
      the core data set, additional parameters can be included if considered essential.

      Registered patients will be provided with diaries for the documentation of feeling of hunger,
      problems and discomforts as well as acetoacetate concentrations in breath. Patients are also
      provided with a portable breath-analyzer to measure acetoacetate concentrations in breath in
      between study visits. Study diaries are collected on Visit 4.

      Data capture will be performed at each study visit after enrollment.
    

Intervention name(s): Fasting; Ketogenic diet
Intervention type(s): Other; Other
Intervention description(s): Acute fasting for 72 hours; Intake of a ketogenic diet for 14 days
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: ADPKD; dietary intervention; ketosis; fasting; ketogenic diet