CORM‐A1 delivers carbon monoxide to the kidney and alleviates post‐ischemic renal dysfunction in rat and swine models

TL;DR

CORM-A1 delivers carbon monoxide to the kidney and improves function after ischemia in rat and swine models.

Contribution

CORM-A1 is shown to effectively deliver CO to peripheral organs and protect against kidney ischemia-reperfusion injury.

Findings

CORM-A1 increased CO levels in blood and kidney tissue after intravenous administration.

CORM-A1 improved renal function and reduced inflammation in rats after 45- and 60-minute ischemia.

In swine, CORM-A1 improved graft function and survival in kidney auto-transplantation.

Abstract

Carbon monoxide (CO), a gas endogenously produced in mammalian tissues, exerts vasodilatory, anti‐ischemic, and anti‐inflammatory effects. These properties have prompted the development of CO‐releasing molecules (CO‐RMs) for therapeutic purposes. Among this class of compounds is CORM‐A1, a boron‐based carboxylic acid, which generates controlled amounts of CO under physiological conditions. In this proof‐of‐principle study we explored the potential of CORM‐A1 to protect kidneys from warm ischemia and reperfusion (WI/R) injury in rat and swine models. We found that intravenous administration of CORM‐A1 significantly increased blood carboxyhemoglobin (COHb) levels while facilitating CO accumulation in renal tissue, thus confirming its ability to deliver CO to peripheral organs. In rats subjected to 45‐ and 60‐min WI/R, administration of CORM‐A1 improved renal function at reperfusion, as shown by decreased serum creatinine and urea levels. Histopathological analysis revealed substantial protection against tubular damage, cell infiltration, and inflammation, especially after 60‐min ischemia. Protection was dose‐dependent, with higher doses offering enhanced effects. In a swine kidney auto‐transplantation model, CORM‐A1 significantly improved graft function, reduced fibrosis and necrosis, and extended graft survival. These findings position CORM‐A1 as a promising CO prodrug, with translational relevance for clinical applications in kidney transplantation and other ischemia‐related conditions.

CORM‐A1 delivers carbon monoxide (CO) to the kidney and improves renal function following warm ischemia‐reperfusion (I/R) in rats and pigs.

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