Published online Dec 24, 2014. doi: 10.5500/wjt.v4.i4.299
Revised: July 8, 2014
Accepted: October 31, 2014
Published online: December 24, 2014
Processing time: 214 Days and 22.3 Hours
AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase (iNOS) inhibitor in a model of donation after circulatory death (DCD) kidneys.
METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective iNOS inhibitor 1400W (10 mg/kg) was administered before reperfusion (n = 6) vs control group (n = 7). Creatinine (1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples.
RESULTS: Kidneys treated with 1400W had a higher level of creatinine clearance (CrCl) [area under the curve (AUC) CrCl: 2.37 ± 0.97 mL/min per 100 g vs 0.96 ± 0.32 mL/min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium (AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400W group after 1 h of reperfusion (1h Pr/Cr: 1400W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400W 139 ± 47 pg/L/mmol/L, P = 0.041].
CONCLUSION: This study demonstrated that 1400W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.
Core tip: It is important to examine the effects of therapies that can reduce ischemia reperfusion injury particularly in donation after circulatory death donor kidneys. The biological role of inducible nitric oxide synthase (iNOS) is somewhat controversial. This study uses a large animal ex vivo model to assess the effects of 1400W, an iNOS inhibitor. The model provides a functional assessment of each kidney, providing a close simulation to clinical transplantation. The study found that 1400W improved early renal function and reduced oxidative stress.