Effect of Weight Loss on Urinary Oxalate Excretion in Obese Calcium Oxalate Kidney Stone Formers

Obese adults (≥19 and ≤ 65 years) with a history of calcium oxalate kidney stone disease will be recruited at both University of Alabama at Birmingham (UAB) and University of Texas South Western (UTSW). Following consent, subjects will complete a screening phase, which includes (1) a meeting with a dietitian to ensure willingness to consume controlled ultra-low oxalate diets and determine anthropometric measurements and blood pressure, (2) collection of fasted blood and 2 x 24-hour urine specimens on self-choice diets to determine general health status and urinary chemistries, respectively, (3) completion of a 7-day run-in diet that includes the use of one serving of an Optifast meal daily to assess tolerance to Optifast VLCD® products. Participants will then consume an eucaloric, ultra-low oxalate controlled diet for 6 days. The controlled dietary phase involves 2 days of dietary equilibration, followed by 2 x 24-hour urine collections, and on the 5th day a dietary oxalate/sucralose oral load. Following the dietary oxalate/sucralose oral load, subjects will have blood collected every 30 minutes and collect 1-hour urines. Participants will then go on an intensive 14-week Optifast VLCD® Program to induce weight loss. At the end of this Optifast VLCD® Program participants will again perform the low oxalate controlled diet and dietary/sucralose oral load study. A total of 40 adult obese calcium oxalate kidney stone formers (20 male and 20 female) will be enrolled (20 at UAB and 20 at UTSW).

Inclusion criteria

• First time or recurrent calcium oxalate stone formers defined as composition of most recent stone >50% calcium oxalate without uric acid component
• Last stone passage or removal greater than 3 months prior to screening
• Body Mass Index (BMI) >35 kg/m2
• Able to provide consent
• Hemoglobin A1C <6.5%
• Normal fasting blood CMP: Normal serum Na, K, Cl, CO2, Calcium, Albumin, AST, ALT <2 times upper limit of normal, Glucose <126 mg/dl, eGFR >60 ml/min/1.73 m2.
• 24-hour urine collection with creatinine within 20% of gender appropriate (mg creat/kg body weight) and consistent between collections (within 20% of each other)
• Willing to ingest menus prepared at the University of Alabama and University of Texas Southwestern Clinical Research Units
• Willing to consume the Optifast VLCD diet
• Willing to ingest menus prepared in Metabolic kitchen. No food allergies or intolerance to any of the foods in study menus. Substitutions for lactose intolerance will be made.
• Willing to avoid vigorous exercise during eucaloric, low-oxalate dietary phase
• Willing to stop use of weight-loss medications
• Willing to stop for 14 days before and during study: medications for stone prevention including diuretics, potassium citrate, allopurinol, febuxostat, and calcium, nutritional, or herbal supplements
• Those with controlled hypertension (systolic blood pressure <160 mmHg, diastolic <90 mmHg) will be included.
• Those without severe dyslipidemia (LDL <200 mg/dL, HDL >30 mg/dL, and triglycerides <250 mg/dL) will be included. Treated and controlled dyslipidemia is accepted
• Smoking/chewing tobacco/vaping will be allowed

Exclusion criteria

• Renal colic or past stone surgery in the past 3 months
• Estimated Glomerular Filtration Rate (eGFR) less than 60 ml/min/1.73m2
• History of type 2 diabetes or screening hgb A1c greater than or equal to 6.5%
• Alcohol or drug abuse. Alcohol consumption >12 units per week and/or unwillingness to abstain from alcohol consumption 2 days before and during the study.
• Mental/medical condition likely to impede study completion
• Current/planned pregnancy or breastfeeding in coming 6 months, unwillingness to use effective method of birth control during the study for individuals of childbearing potential.
• Planned vacation in coming 4 months
• Febrile illness including flu/common cold/COVID-19 within 21 days of study start
• Primary or enteric hyperoxaluria
• Gastrointestinal disorder or surgery that impacts oxalate transport
• Cirrhosis, pancreatic or biliary disorder, porphyria, gout
• Malignancy treated within the past 12 months
• Nephrotic syndrome, neurogenic bladder, urinary diversion
• History of primary hyperparathyroidism, cystinuria, renal tubular acidosis, sarcoidosis, cystic fibrosis
• Uncontrolled hypertension, myocardial infarction in past 6 months, unstable angina, congestive heart failure
• Medications: Topiramate, acetazolamide, zonisamide, diuretics, SGLT2-inhibitors, immunosuppressants