Sildenafil has been used as a pre-conditioning agent to protect against ischaemic kidney injury in a porcine cardio-pulmonary bypass model (Patel NN et al, Ann Thorac Surg2011; 92(6):2168-76), although there is little evidence for its benefit in reducing ischaemia reperfusion (I/R) injury in renal transplantation. The aim of this study was to assess the effects of sildenafil on I/R injury in a porcine model of donation after circulatory death (DCD) kidneys.
Kidneys were subjected to 20 minutes warm ischaemia followed by 18 hours cold storage. After preservation kidneys were reperfused on an ex vivo perfusion system for 3 hours with an oxygenated blood based solution. Kidneys were treated with 0.2mg (n=4), 0.7mg (n=4), 1.4mg (n=6) or no (control, n=6) sildenafil during reperfusion. Renal function and renal injury markers were measured throughout reperfusion.
Renal blood flow was increased in a dose dependent manner with a significantly higher flow in the 1.4mg treated kidneys compared to the controls [mean area under flow-time curve (AUC), (1.4mg) 482±99, (0.7mg) 469±123, (0.2mg) 387±115, (Control) 360 ± 47ml/min/100g; P=0.021]. There was no significant improvement in creatinine clearance; [AUC (1.4mg) 2.9±0.8, (0.7mg) 2.5±0.6, (0.2mg) 3.0±2, (control) 4.5±2.0ml/min/100g], tubular injury [neutrophil gelatinase-associated lipocalin (NGAL)], levels of inflammatory cytokines (IL-6 and TNFΑ) or neutrophil infiltration between the groups.
Sildenafil had a vasodilatory action but did not affect recovery of renal function or protect against I/R injury. This suggests that sildenafil is not renal protective during the early reperfusion phase in an ex vivo DCD model. One possible explanation for the lack of effect on creatinine clearance maybe the sildenafil induced efferent arteriole vasodilatation, reducing filtration.
To cite this abstract in AMA style:Randle L, Hosgood S, Patel M, Watson C, Bradley J, Nicholson M. Sildenafil Enhances Renal Blood Flow but Does Not Protect Against Ischaemia Reperfusion Injury in a Model of Donation after Circulatory Death Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/sildenafil-enhances-renal-blood-flow-but-does-not-protect-against-ischaemia-reperfusion-injury-in-a-model-of-donation-after-circulatory-death-kidney-transplantation/. Accessed November 23, 2020.
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