Oxalate and Citrate in Humans

Experimental Design and Implications Administration of oral oxalate without citrate will determine the contribution of diet to this association. We will measure fractional excretion of oxalate and citrate. Both are freely filtered by the glomerulus and either secreted or reabsorbed (oxalate) or just reabsorbed (citrate). We will be able to assess urine excretions partitioned from the contribution of the filtered load and subsequent tubule handling by using fractional excretion.

This study has large implications for both patient care and future studies. If the urine oxalate-citrate association is primarily related to dietary oxalate and citrate, then fractional excretion of citrate will not increase after our proposed isolated dietary oxalate load test in controls or stone formers. This observation will allow practitioners to consider this when developing diets for kidney stone prevention and consider recommending consuming foods high in citrate (or supplementing alkali) simultaneous with oxalate consumption. In addition, the results of this experiment will lead to future studies including alkali supplementation prior to the oxalate load test to see if urine oxalate-citrate balance can be restored. If the oxalate-citrate association is not solely driven by diet, we anticipate a rise in fractional excretion of citrate and a difference in the urinary oxalate-citrate relationship between non-stone formers and stone formers. If so, this association may be related to SLC26Ac/NaDC-1 gene linkage and its potential disruption in stone formers. This may lead to future genetic and drug studies related to regulation of these transporters. Finally, differences in urinary oxalate-citrate association between non-stone-formers and stone formers may be a related to disordered acid-base handling that contributes to the blunted association in stone formers and further observed in those with Roux-en-Y Gastric Bypass. Much of the work on disordered acid-base handling in stone formers has been done by Drs. Worcester and Coe. Therefore, a future study providing supplemental alkali with oxalate containing foods may provide additional insight into stone risk mechanisms for these patients.

APPROACH Experimental Design: Studies will be carried out in the University of Chicago Medicine (UCM) Clinical Research Center (CRC).

Informed Consent Process: Subjects will be taken through the informed consent process by myself or the study research assistant. Subjects will be given ample time to discuss and ask questions. No study activities will occur until after the subject has signed the consent form.

In non-stone-formers (N=25) and non-obese calcium/oxalate stone-formers(N=25), give an oral (360mg) sodium oxalate load and measure both urine and serum oxalate and citrate over six hours. Primary endpoint (hypothesis 1a) is change from baseline in fractional excretion of citrate adjusted for change in fractional excretion oxalate after oxalate load. Secondary endpoint (hypothesis 1b) is to compare change in fractional excretion of citrate adjusted to fractional excretion oxalate in non-obese stone-formers versus non-stone-formers.