Insulin maintains plasma antioxidant capacity at an early phase of kidney transplantation

Abstract

Ischaemia-reperfusion and hyperglycaemia are two main sources of oxidative stress that plays an important role in the pathophysiology of tissue injury in transplant recipients. We hypothesized that controlling hyperglycaemia with insulin during the first hours following kidney transplantation could improve antioxidant defences and therefore decrease ischaemia-reperfusion-induced injury. We performed a prospective randomized study in non-diabetic dialysed patients receiving a first cadaveric renal allograft, and assigned them to receive either 200 g/day of glucose infusion (control group, n=23) or the same glucose infusion and intravenous insulin to maintain blood glucose<10 mmol/l (insulin group, n=20). Antioxidant defences were assessed by the plasma total radical-trapping antioxidant parameter (TRAP). TRAP values remained stable throughout the study in the Insulin group, whereas they decreased from admission to day 1 (-2.70+/-0.16 vs -2.98+/-0.26, P<0.0001), and tended to retrieve the basal values at day 15 in the control group. TRAP values were significantly higher in the insulin group compared with the control group at days 1 (-2.80+/-0.19 vs -2.98+/-0.16, P<0.05) and 4 (-2.80+/-0.19 vs -2.95+/-0.20, P<0.05). No differences were found between the two groups on urinary malondialdehyde determination, two markers of oxidative damage, nor in graft function or patient outcome. This is the first clinical trial to demonstrate improvement in insulin-induced antioxidant defences at the early stage of kidney transplantation. More extensive studies will tell if this strategy has beneficial impact in long-term graft outcome.