Gut–kidney axis in oxalate homeostasis

Purpose of review The gut–kidney axis plays a critical role in oxalate homeostasis, and better understanding of oxalate transport regulatory mechanisms is essential for developing novel therapies. Recent findings Oxalate potentially contributes to chronic kidney disease (CKD) progression, CKD - and end stage renal disease (ESRD)-associated cardiovascular diseases, polycystic kidney disease (PKD) progression, and/or poor renal allograft survival, emphasizing the need for plasma and urinary oxalate lowering therapies. One promising strategy would be to enhance the bowel's ability to secrete oxalate, which might be facilitated by the following findings. Oxalobacter formigenes (O. formigenes) -derived factors recapitulate O. formigenes colonization effects by reducing urinary oxalate excretion in hyperoxaluric mice by inducing colonic oxalate secretion. Protein kinase A activation stimulates intestinal oxalate transport by enhancing the surface expression of the oxalate transporter SLC26A6 (A6). Glycosylation also stimulates A6-mediated oxalate transport. The colon adapts to chronic acidosis in rats through increased colonic oxalate secretion as previously reported in CKD rats, and A6-mediated enteric oxalate secretion is critical in reducing the body oxalate burden in CKD mice. Intestinal oxalate transport is negatively regulated by proinflammatory cytokines and cholinergic, purinergic, and adenosinergic signaling. Summary These findings could facilitate the development of novel therapeutics for hyperoxalemia, hyperoxaluria, and related disorders if similar regulatory mechanisms are confirmed in humans.