Category: Basic Science: Stones
Introduction & Objective : Studies have demonstrated the positive correlation between body weight/BMI and urinary oxalate excretion. We hypothesize that this is due to increased endogenous oxalate synthesis. This was studied in two models of obesity, ob+/ob+ mice and wild type mice fed a high fat diet.
Methods : Wild type (WT) controls (n=5), high fat diet (HFD) (n=5), ob+/ob- lean controls (n=3), and ob+/ob+ (n=3) mice were fed a diet ultra-low in oxalate (<10µg/g diet) and glycolate (<3µg/g diet) and housed in metabolic cages. In the high fat diet, 45% of calories was fat vs 17% in normal diet. While on controlled diets the WT and HFD mice were administered a subcutaneous bolus of 2 µmoles 13C2-glycolate (oxalate precursor). 24 hour urine samples were collected. Ion chromatography coupled with mass spectroscopy was used to measure oxalate and glycolate isoptomers.
Results : HFD mice weight compared to control was 42.1 g vs 30.5 g (p=0.0002). 24 hour urinary oxalate excretion indexed to urinary creatinine (Cr) was significantly higher in the ob+/ob+ mice and the HFD mice relative to the comparative control mice, 303.3 vs 95.6 µg/mg Cr (ob+/ob+ versus ob+/ob-),p=0.01 and 133.1 vs 106.2 µg/mg Cr (HFD versus WT), p=0.003. 24 hour urinary glycolate excretion was also significantly higher in each, 289.5 vs 105.0 µg/mg Cr (ob+/ob+ versus ob+/ob-),p=0.0001 and 193.1 vs 166.2 (HFD versus WT ), p=0.05. HFD mice produce more oxalate from glycolate following subcutaneous injection as measured by 13C2-oxalate levels, 1.5 vs 1.0 µg Cr, p=0.04.
Conclusions : These findings suggest that obesity increases endogenous oxalate synthesis. Further studies are needed to understand the metabolic changes that occur in obesity.
Kyle Wood– Assistant Professor, University of Alabama at Birmingham, Birmingham, Alabama
John Knight– Assistant Professor, University of Alabama at Birmingham, Birmingham, Alabama
Ross Holmes– Professor, University of Alabama at Birmingham, Birmingham, Alabama
Dean Assimos– Professor, University of Alabama at Birmingham, Birmingham, Alabama
University of Alabama at Birmingham
Kyle David Wood MD is an Assistant Professor at the University of Alabama at Birmingham. He has completed an Endourology Fellowship. His clinical practice is focused on the medical and surgical management of complex kidney stones. He was an AUA Research Scholar and recently recieved a K08 NIH mentored grant. His research interest is on endogenous oxalate synthesis and its relationship to kidney stone disease.
University of Alabama at Birmingham
Dr. Dean George Assimos is currently the Anton J. Bueschen Professor and Chairman of the Department of Urology at the University of Alabama at Birmingham School of Medicine. He obtained a BS degree in biology from Purdue University in 1974 and an MD degree from Loyola University of Chicago in 1977. He subsequently completed his urology residency at Northwestern University in 1983. He was a fellow in intra-renal surgery and kidney stone disease at Wake Forest University in 1984 after which he was an A.U.A. research scholar at the same institution from 1984-1986. He has dedicated his career to the care of patients afflicted with complex renal stone disease including medical and surgical management. He has conducted clinical, translational and basic science research focusing on factors which impact urinary oxalate excretion. He and his research colleagues have received steady funding from the NIH for these endeavors. They have demonstrated the important contribution of dietary oxalate to the urinary oxalate pool, defined the importance of interactions between dietary calcium and oxalate, and characterized mechanisms of gastrointestinal oxalate absorption and endogenous oxalate synthesis. He is the author of numerous papers and chapters pertaining to these subjects. He has served as a member of the A.U.A Nephrolithiasis Guidelines and was the Chair of this committee. Dr. Assimos is on the editorial board of several urologic journals. He is also committed to urologic education participating as a speaker and course director for the A.U.A. and other organizations. He has received several prestigious honors including the American Urological Care Foundation Distinguished Scholar Alumnus Award, the Ralph Clayman Mentor Award from the Endourological Society, and the AUA Hugh Hampton Young Award. Dr. Assimos is the past president of the Southeastern Section of the A.U.A.