Renal ischemic postconditioning in a laparoscopic porcine model

Abstract

Background: During procedures such as nephron sparing surgery, kidney transplantation and thorocoabdominal aorta aneurysm surgery the kidney is subjected to ischemia and reperfusion injury which may lead to loss of renal function. It has been proposed that an intermittent and brief repeated sequence of ischemia and reperfusion immediately after the main ischemic insult, known as ischemic postconditioning (IPoC) may protect the kidney from ischemic/reperfusion injury. The aim of the study was to evaluate an IPoC protocol in an in vivo porcine model of warm ischemic injury with 75 minutes occlusion of the left renal hilum followed by 48 hours reperfusion. Method: 16 hybrid pigs were randomised to either warm renal ischemia only (control) or warm renal ischemia followed by 6 x 15 seconds IPoC prior to laparoscopic surgery. Following anesthesia, the left kidney hilum was clamped for 75 minutes and the intervention group then received 6 x 15 seconds postconditioning. Serum creatinine and urea was measured following 24 hours and 48 hours respectively. Blood was analysed for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and tumor necrosis factor alpha (TNFα). Just before 48 hours of reperfusion, urine was collected from each kidney separately for 60 minutes and sampled for analysis of NGAL. Urinary biomarker analysis of uNGAL and uKIM-1 was conducted between three groups: sham right kidney, IR left kidney, and IPoC left kidney. Results: Having only IR or IPoC significantly decreased corrected creatinine clearance (corCrCl) compared to not receiving an intervention (p<0.001). The IPoC group (n=4) had a higher corCrCl after 48 hours of reperfusion compared to the IR only group (n=3) (p= 0.04). There was a significant increase in uNGAL in IR group from PreOp to POD 2 (p=0.02). There was a significant effect of IR and IPoC on levels of uNGAL compared to sham right kidney (p=0.001). Having only IR or IPoC significantly increased uNGAL compared to receiving no IR (p=0.003). Conclusion: Preliminary results suggest that ischemic postconditioning attenuates warm ischemia/ reperfusion injury in a laparoscopic double kidney porcine model of warm ischemia.