Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion

Abstract

Kidney stone disease is increasing in prevalence, and the most common stone composition is calcium oxalate. Dietary oxalate intake and endogenous production of oxalate are important in the pathophysiology of calcium oxalate stone disease. The impact of dietary oxalate intake on urinary oxalate excretion and kidney stone disease risk has been assessed through large cohort studies as well as smaller studies with dietary control. Net gastrointestinal oxalate absorption influences urinary oxalate excretion. Oxalate-degrading bacteria in the gut microbiome, especially Oxalobacter formigenes, may mitigate stone risk through reducing net oxalate absorption. Ascorbic acid (vitamin C) is the main dietary precursor for endogenous production of oxalate with several other compounds playing a lesser role. Renal handling of oxalate and, potentially, renal synthesis of oxalate may contribute to stone formation. In this review, we discuss dietary oxalate and precursors of oxalate, their pertinent physiology in humans, and what is known about their role in kidney stone disease.

Keywords: calcium oxalate; dietary oxalate; kidney stones; metabolism; nephrolithiasis; oxalate; oxalate synthesis; urolithiasis.

Figure 1

Pathways of endogenous oxalate synthesis. Synthesis of oxalate occurs via enzymatic (names in italics) and non-enzymatic reactions taking place in different subcellular compartments (cytosol, mitochondria, and peroxisome). The molecular formula is given in brackets underneath each compound. Glycolaldehyde is a product of fructose and xylitol metabolism. 1P5C: 1-pyrroline-3-hydroxy-5-carboxylic acid, LDH: lactate dehydrogenase, GO: glycolate oxidase, GR: glyoxylate reductase, AGT: alanine:glyoxylate aminotransferase, DAO: D-amino oxidase, ALDH: aldehyde dehydrogenase, GLO: glyoxalase, HOGA: 4-hydroxy-2-oxoglutarate aldolase, AspAT: aspartate aminotransferase, 1P5CDH: 1P5C dehydrogenase, HYPDH: 4-hydroxyproline dehydrogenase.