Renoprotective effects of gut NHE3 inhibitor tenapanor in a rat model of unilateral renal ischemia–reperfusion injury with contralateral nephrectomy

Kidney ischemia–reperfusion (I/R) injury is an unavoidable complication of kidney transplantation that contributes to acute kidney injury (AKI), chronic kidney disease (CKD), and limited long-term graft survival. Elevated serum phosphate has been implicated not only as a consequence of renal dysfunction but also as an active mediator of kidney injury. Tenapanor, an intestinal sodium/hydrogen exchanger 3 inhibitor approved for the treatment of hyperphosphatemia in dialysis patients, may therefore have renoprotective potential; however, its effects on renal I/R injury remain unclear. Here, we show that oral administration of tenapanor suppresses renal calcium phosphate deposition after I/R, mitigates AKI progression, and reduces subsequent renal fibrosis in rats. These findings suggest that tenapanor mitigates renal I/R injury and may represent a potential pre-transplant strategy to improve long-term graft outcomes.