Gut Oxalate Transport and Gut Microbiome as Potential Therapeutic Targets for Hyperoxaluria and Hyperoxalemia: Implications for Related Human Disease.

Abstract

Besides kidney stones (KS), oxalate potentially contributes to chronic kidney disease (CKD) and its progression, CKD- and end stage kidney disease (ESKD)-associated cardiovascular diseases, and poor kidney transplant survival. KS affect about 1 in 5 men and 1 in 11 women and the recurrence rate remains high (50% in 5 years and up to 80% in 10-20 years), reflecting that current interventions are inadequate, and novel therapies are needed. 70-80% of KS are composed of calcium oxalate and small increases in urine oxalate enhance the KS risk. The gastrointestinal tract (gut) plays a major role in oxalate homeostasis by acting as a site for oxalate absorption and secretion. Therefore, the gut potentially represents a novel therapeutic pathway for body oxalate elimination. Strategies aiming at reducing the gut's ability to absorb oxalate and/or enhancing its ability to secrete oxalate can lead to decreased plasma and urinary oxalate levels and therefore can serve as novel approaches for the prevention and/or treatment of hyperoxalemia and hyperoxaluria. Humans lack oxalate metabolizing enzymes, and they rely on gut bacteria referred to as oxalate-degrading bacteria (oxalobiome) for gut oxalate degradation. This limits net gut oxalate absorption, thereby helping with maintaining normal oxalate homeostasis. This review focuses on the role of gut oxalate transport and gut microbiome in overall oxalate homeostasis and how they can be therapeutically targeted. Importantly, the majority of evidence for gut oxalate transport is derived from animal studies, but the relevance of these findings to human gut oxalate transport remains to be established.