Ketogenic Dietary Patterns in Young Adults and Kidney Health

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.

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.

Eligibility Criteria:
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