Renal Metabolism of Glycolate to Oxalate

It is known that glycolate, an intermediary molecule in normal metabolism, can be converted into oxalate. The origin of urinary oxalate is of interest as calcium oxalate is a main component of kidney stones. In the rare disease primary hyperoxaluria, excessive production of oxalate by the body results in frequent kidney stones and can cause loss of kidney function. Primary hyperoxaluria is caused by deficiencies in one of several enzymes involved in the glycolate pathway.

This study will seek to determine how much oxalate is formed from glycolate in normal subjects. After consuming a controlled diet, subjects will either ingest or have an intravenous infusion of carbon 13 glycolate, a stable isotope of glycolate that can be tracked and will also label downstream metabolic products. Blood and urine samples will be assessed for their amounts of labeled glycolate and labeled oxalate to provide an accurate measure of how much oxalate is made from normal glycolate breakdown in healthy human subjects.

Inclusion criteria

• Mentally competent adults, able to read and comprehend the consent form
• 18-75 years of age
• Body Mass Index (BMI) between 19 and 40
• In good health as judged from a medical history, reported medications, and a complete blood metabolic profile
• Acceptable 24 hour urine collections (performed twice for screening)

Exclusion criteria

• History of any hepatic, renal, bowel, or endocrine disease or any other condition that may influence the absorption, transport or urine excretion of ions
• Abnormal urine chemistries or blood metabolic profiles
• Poor 24 hour urine collections completed during screening, judged by 24 hour urine creatinine excretion (indicative of not collecting all urine in the 24 hour period)
• Pregnancy, intention to become pregnant in the near future, or lactation
• Aged <18 or >75
• BMI <19 or >40