The Relative Effects of Warm and Cold Ischemic Injury in an Experimental Model of Nonheartbeating Donor Kidneys

Abstract

Ischemia reperfusion injury (I/R) leads to delayed graft function and remains an important problem in renal transplantation. The aim of this experimental study was to assess the effects of warm (WI) and cold ischemia (CI) in models of heartbeating (HBD) and controlled/uncontrolled nonheartbeating donor (NHBD) kidneys. A reperfusion model utilizing cardiopulmonary bypass technology was used to perfuse isolated porcine kidneys with autologous blood after the following conditions: 0 min WI+2 h cold storage (CS); 0 min WI+18 h CS; 10 min WI+2 h CS; 10 min WI+18 h CS; 25 min WI+2 h CS; 25 min WI+18 h CS. Renal function was measured over a period of 3 hr. Renal functional parameters were not significantly different between 0, 10, 25 WI with 2 h CS [AUC creatinine (Cr) decrease of 1057+/-177, 1102+/-260, and 1245+/-143 micromol/L h, P=0.338; AUC creatinine clearance (CrCl) of 37.7+/-15.8, 36.2+/-21.7, 19.8+/-9.1 ml/min/100 g h, P=0.099]. After 18 h CS, renal function was severely impaired in the 10 and 25 WI groups compared to 0 min WI [AUC Cr of 2156+/-401, 2287+/-148, 1563+/-395 micromol/L h, P=0.037; AUC CrCl of 2.2+/-1.7, 1.5+/-1.5, 21.7+/-13.4 ml/min/100 g h, P=0.007). Warm ischemia of up to 25 min was only detrimental to renal function when kidneys were subsequently preserved in cold storage for 18 hr. This data suggests that limiting the cold storage period is of paramount importance when transplanting kidneys subjected from nonheartbeating donors.