Ketogenic Dietary Patterns in Young Adults and Kidney Health

Study Overview
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Brief Summary
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This study seeks to assess the kidney health effects of short-term healthful ketogenic diet in young, overweight adults.10 overweight (BMI 25-30 kg/m2) adult participants (ages 20-40 years) without major chronic conditions including diabetes, kidney, cardiac, or liver disease will receive an isocaloric, high protein and low carbohydrate ketogenic diet for 2 weeks.

Detailed Description
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After baseline measures are taken, 10 overweight (BMI 25-30 kg/m2) young adult participants (ages 20-40 years) without major chronic conditions including diabetes, kidney, cardiac, or liver disease will receive an isocaloric, high protein and low carbohydrate ketogenic diet for 2 weeks. Each participant will consume one meal daily in the Diet and Nutrition (DAN) laboratory metabolic kitchen at the University of Virginia (UVA) and receive the remainder of the daily food allocation packed out to consume at home. Plate-waste method and NDS-R software will be used to measure food consumption (all served and packed-out foods and all uneaten and returned portions will be weighed). Weight, blood pressure and symptom surveys will be monitored at least 3 times a week. Fasting blood and 24 hour urine samples will performed at baseline and the end of each week. Stool for microbiota will be assess at baseline and end of study. Adherence will be confirmed with urinary biomarkers (e.g. urinary nitrogen) and point of care blood testing ketones. Differences in estimated glomerular filtration rate (GFR) determined from serum creatinine and cystatin C will be evaluated for each participant to assess magnitude of increase in GFR on the ketogenic diet. Over the past decade new panels of biomarkers have become available measuring glomerular permeability (urine albumin to creatinine ratio; UACR) and kidney injury and repair (IL-18, kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], liver fatty acid type binding protein [L-FABP], tumor necrosis factor α [TNF-α, TNF receptor 1 and 2], transforming growth factor beta [TGF-β], human cartilage glycoprotein 39 [YKL-40], and monocyte chemoattractant protein 1 [MCP-1]). Change in UACR comparing the end of two weeks to baseline will be the primary outcome. Changes in other kidney injury markers will be assessed as secondary and exploratory outcomes. Additional exploratory outcomes will include urine metabolomics and stool 16S rRNA to characterize the gastrointestinal microbiota. Biosamples will be stored in a repository for future uses.

Official Title
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Ketogenic Dietary Patterns in Young Adults and Kidney Health

Conditions
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Ketogenic Diet, Kidney Injury

Intervention / Treatment
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* Behavioral: Ketogenic Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight (BMI 25-30 kg/m2) Weight stable for last 4 weeks by self-report Residing in the greater Charlottesville/Albemarle area for >6 months out of the last year Normal kidney function at baseline, eGFR ≥60 ml/min/1.73m2 and UACR <30 mg/g at screening Exclusion Criteria: History of major medical comorbidities by self-report (history of diabetes; diagnosed kidney disease; diagnosed gastrointestinal disorders including inflammatory bowel disease, gastric bypass, intestinal resection, celiac disease or other malabsorption; esophageal or other disorders limiting ability to swallow food) Systolic blood pressure >160 or <100 at screening Daily use of diuretics such as hydrochlorothiazide Serum potassium <3.5 or >5.1 mEq/L at screening Serum magnesium <1.6 mg/dL at screening Serum sodium <135 or >149 mEq/L at screening HbA1c > 6.5% at screening Fasting plasma glucose > 126 mg/dL at screening Pregnant or breastfeeding women (confirmed by spot urine at screening) Inability to give written informed consent in English Inability to walk up to 1 mile at a slow pace between buildings for study visits Food allergies Eating ketogenic or low carbohydrate diet over last 4 weeks Blood ketones positive at screening Intolerance or dislike of any study foods limiting adherence Inability to attend daily visits Vulnerable population such as direct reports or students of the investigators Lack of access to refrigeration or equipment to safely reheat meals

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet<br>Subjects will be provided with foods following a ketogenic diet for 15 consecutive days. | Behavioral: Ketogenic Diet<br>* 2 week isocaloric, high protein and low carbohydrate ketogenic diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-person change in UACR comparing Day 15 to pre-intervention | Urine Albumin-Creatinine Ratio comparison tested at alpha 0.05 | Day 0 and day 15 of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Within-person change in eGFR-Cr comparing Day 15 to pre-intervention | Tested at alpha 0.0125, corrected (Bonferroni correction) for 4 overall outcomes. Due to very high correlation between different eGFR equations these are not corrected as independent tests | Day 0 and day 15 of the intervention | 
| Within-person change in eGFR-Cystatin comparing Day 15 to pre-intervention | Tested at alpha 0.0125, corrected (Bonferroni correction) for 4 overall outcomes. Due to very high correlation between different eGFR equations these are not corrected as independent tests | Day 0 and day 15 of the intervention | 
| Within-person change in eGFR-Cr-and-Cystatin comparing Day 15 to pre-intervention | Tested at alpha 0.0125, corrected (Bonferroni correction) for 4 overall outcomes. Due to very high correlation between different eGFR equations these are not corrected as independent tests | Day 0 and day 15 of the intervention | 
| Within-person change in urine KIM-1 comparing Day 15 to pre-intervention | Tested at alpha 0.0125, corrected (Bonferroni correction) for 4 overall outcomes. Due to very high correlation between different eGFR equations these are not corrected as independent tests | Day 0 and day 15 of the intervention | 
| Within-person change in urine NGAL comparing Day 15 to pre-intervention | Tested at alpha 0.0125, corrected (Bonferroni correction) for 4 overall outcomes. Due to very high correlation between different eGFR equations these are not corrected as independent tests | Day 0 and day 15 of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, kidney injury