High-Oxalate Diets Increase Urinary Oxalate Excretion and Nanocrystalluria in Healthy Adults and Calcium Oxalate Kidney Stone Formers

Background: Kidney stones (KS) affect approximately 10% of the United States population. The majority of KS are comprised of calcium oxalate (CaOx). Urinary oxalate is derived from dietary sources as well as endogenously synthesized. It may exist in soluble or crystalline forms in urine. We recently developed a novel method to detect and quantify nanocrystals in urine. We previously reported that a single dietary oxalate load augments urinary oxalate output and nanocrystalluria in healthy adults within 5 hours. The aim of this study was to determine whether increasing dietary oxalate augments urinary oxalate excretion and nanocrystalluria in CaOx KS formers (CaOx KSF) and healthy adults. Methods: Sixteen healthy adults without a history of KS and 6 CaOx KSF adults were randomly assigned to consume one of two controlled diets: (50 mg oxalate and 800 mg of calcium/day) or (250 mg oxalate and 800 mg of calcium/day) for 4 days. After a 10-day washout period, they consumed the other diet for 4 days. Urine was collected on the last day of both dietary regimens. Urinary oxalate excretion and the number of nanocrystals were characterized using ion-chromatography-mass spectrometry and nanoparticle tracking analysis, respectively. Microscopy and spectroscopy were used to evaluate morphology and chemical crystal composition. Results: Both cohorts had increased urinary oxalate excretion while consuming the higher oxalate containing diets compared to the lower oxalate containing diets (Healthy adults – low 6.23 ± 0.80 vs high 13.46 ± 1.46 mg oxalate/g Cr, p<0.007; CaOx KSF – low 7.81 ± 0.59 vs high 13.67 ± 2.03 mg oxalate/g Cr, p<0.069). In addition, nanocrystalluria was significantly elevated (Healthy adults – low 1.39E+08 ± 2.65E+07 vs high 3.00E+08 ± 4.02E+07 particles/mL, p=0.008; CaOx KSF – low 1.91E+08 ± 3.98E+07 vs high 3.90E+08 ± 7.00E+07, p=0.049). Microscopy revealed that the nanocrystals had CaOx morphology, and spectroscopy confirmed that they were composed of CaOx. Conclusion: These findings suggest that intake of meals containing moderate/large amounts of oxalate augments urinary oxalate excretion and promotes nanocrystalluria, which is more profound in CaOx KSF. Such responses may play a role in KS formation and could be a potential marker for KS risk. Funding: NIDDK Support