Early Urinary Biomarkers of Warm and Cold Ischemic Injury in an Experimental Kidney Model

Abstract

Early urinary biomarkers may be useful in determining the severity of ischemic injury in donation after circulatory death (DCD) kidneys. The aim of this study was to evaluate the efficacy of a collective series of urinary biomarkers in relation to the warm and cold ischemic intervals. Porcine kidneys were retrieved after 0, 10, and 25 min of warm ischemia (WI), then preserved by static cold storage (CS) for period of 2 and 18 h. After preservation, kidneys were reperfused on an isolated organ perfusion system to assess renal function and injury. Levels of IL-6, TNFα, endothelin-1 (ET-1), and neutrophil gelatinase-associated lipocalin (NGAL) were measured in urine samples after 3 h of reperfusion. There was no significant difference in renal functional parameters or urinary biomarkers between the WI times when kidneys were stored for 2 h (P > 0.05). After 18 h CS, kidneys with 10 and 25 min of WI demonstrated a significant decline in renal function compared with kidneys without WI (P < 0.05). Levels of ET-1 and NGAL were significantly higher in kidneys with 25 min WI (25 m ET-1, 30.1 ± 21.2, versus 0 m 2.25 ± 1.5 pg/mL; P = 0.002: NGAL, 25 m 77 ± 51 versus 0 m 10 ± 0.1 pg/mL; P = 0.005). Levels of IL-6 and TNFα were significantly higher in kidneys with 10 and 25 min of WI (P = 0.001, 0.001). Early urinary biomarkers are a useful means to determine graft injury. ET-1 and NGAL are more accurate in predicting the severity of ischemic injury compared with inflammatory markers.