BACKGROUND.: CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl that liberates carbon monoxide under appropriate conditions. Carbon monoxide exerts effects on intracellular apoptotic and inflammatory pathways, which suggest a role in reducing the effects of renal ischemia/reperfusion (I/R) injury. This study investigated the effects of CORM-3 administered at the time of reperfusion in a model of controlled nonheartbeating donor kidneys. METHODS.: Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 muM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 muM), and control (no further intervention). Renal hemodynamics and function were then measured during 3-hr reperfusion with autologous blood using an isolated organ-perfusion system. RESULTS.: CORM-3 at a concentration of 50 muM improved renal blood flow (RBF) compared with the iCORM and control groups (area under the curve 774+/-19 vs. 448+/-88 vs. 325+/-70, respectively, P=0.002). CO-releasing molecule-3 at a concentration of 50 muM also improved renal function during reperfusion with a greater area under the curve for creatinine clearance (CORM-3: 14+/-6 vs. iCORM: 3.3+/-0.1 vs. control: 2.2+/-2 mL/min, P=0.006) and higher urine output (CORM-3: 793+/-212 vs. iCORM: 368+/-72 vs. control: 302+/-211 mL, P=0.01). CO-releasing molecule-3 at a concentration of 100 muM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 muM) led to poor renal hemodynamics and function after reperfusion. CONCLUSION.: Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.

Bagul A, Hosgood SA, Kaushik M, Nicholson ML.

Department of Transplant Surgery, University Hospitals of Leicester, Leicester, United Kingdom.