This study will determine the contribution of glycolate metabolism to urinary oxalate excretion in healthy subjects, using carbon 13 isotope glycolate tracer technique and a low-oxalate controlled diet.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
Participants will consume a diet that is controlled in its contents of protein, carbohydrates, fat, calcium, oxalate, vitamin C and sodium. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.
Participants will receive a continuous intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, over the course of several hours until steady-state is achieved, using an IV catheter.
University of Alabama at Birmingham
Birmingham, Alabama, United States
Urinary oxalate measured by ion chromatography coupled with mass spectrometry
Measurement of carbon 13 labeled and unlabeled urinary oxalate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
Time frame: day 5 of dietary control
Plasma glycolate measured by ion chromatography coupled with mass spectrometry
Measurement of carbon 13 labeled and unlabeled plasma glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
Time frame: day 5 of dietary control
Urinary creatinine
Baseline assessment of 24hr urinary creatinine under controlled low-oxalate diet.
Time frame: day 5 of dietary control
Urinary glycolate measured by ion chromatography coupled with mass spectrometry
Measurement of carbon 13 labeled and unlabeled urinary glycolate following carbon 13 glycolate administration, after equilibration under a low-oxalate diet.
Time frame: day 5 of dietary control
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Participants will receive a bolus intravenous administration of carbon-13 glycolate, a naturally occurring form of glycolate, using an IV catheter.
Participants will orally ingest a single dose of carbon-13 glycolate, a naturally occurring form of glycolate.