Effects of urodilatin on renal graft blood flow during ischemia-reperfusion syndrome in a pig autotransplant model

Abstract

FTER KIDNEY PROCUREMENT, during the period of renal ischemia, vasoactive substances are released. During reperfusion of the graft, oxygen free radicals are formed and renal resistances increased. The kidney suffers ischemia-reperfusion injury and intrarenal vasoconstriction. This vascular situation is probably a major cause of delayed graft function, which may increase postoperative morbidity. Alterations in microvascular perfusion are particularly important. Urodilatin is a natriuretic peptide isolated from human urine with a major role in regulation of renal sodium and water excretion. 1 Additional microvascular renal effects, mainly dilatation of afferent renal arterioles and constriction of efferent ones, could be beneficial in the prevention of the ischemia-reperfusion syndrome. 2 We have evaluated the effects of urodilatin administration on main renal graft artery flow just after revascularization. METHODS Eleven male hybrid commercial pigs underwent right nephrectomy on day 0. Kidneys were flushed with Wisconsin solution and stored at 4°C for 24 hours. Contralateral nephrectomy with orthotopic renal transplantation (with the graft previously preserved) was performed on day 1. The period of warm ischemia time was around 40 minutes and the urinary tract was restituted with ureteroureteral suture. Monitoring included continuous arterial pressure through femoral probe and continuous renal graft blood flow (RGBF), with an electromagnetic probe placed on main renal graft artery at the time of revascularization. Urodilatin (HaemoPep Pharma GmbH, Hannover) was infused IV through an ear vein in six animals (bolus just after revascularization and infusion over 45 minutes thereafter) on a dose-finding fashion: bolus 4 ug/kg/min and infusion 1 ug/kg/min (n 1), 2 ug/kg/min and infusion 0.5 ug/kg/min (n 2), and 1 ug/kg/min and infusion 0.3 ug/kg/min (n 3). In control pigs, normal saline was infused in a similar amount.