Ascorbic acid against reperfusion injury in human renal transplantation

Abstract

The cadaveric renal graft is exposed to ischaemic injury during preservation and to oxidative damage during reperfusion. Both these mechanisms are known to cause cell damage, which may impair graft function. Reperfusion injury (RPI) is mediated by reactive oxygen species (ROS). Ascorbic acid (AA) is a potent physiological extracellular scavenger of ROS. We perfused 31 renal grafts immediately before implantation with a solution of Euro-Collins containing 0.5 mg/ml of AA to diminish RPI. From every donor, the contralateral kidney served as a control. The control grafts were perfused with the same perfusion as those of the AA group, only without the AA substitution. We assessed the effect of AA by recording serum creatinine, creatinine clearance, initial graft function and early rejections. The incidence of delayed graft function (DGF) was 32% in the AA group, and 29% in the control group. Other parameters were also similar in both groups, except for the length of DGF, which showed a trend towards a shorter duration in the AA group. The pre-operative systemic AA concentration was significantly ( P=0.01) lower in the haemodialysis patients than in those on peritoneal dialysis. In conclusion, this clinical study could not demonstrate significant benefits of AA in renal transplantation.

Vitamin C activation of the biosynthesis of epoxyeicosatrienoic acids

“…Hemodialysis patients exhibit reduced systemic concentrations of VitC and VitC diminishes reperfusion injury in patients undergoing renal transplantation [36,37]. Based on microsomal VitC-dependent EET formation, and the vasodilator properties of EETs in the kidney, we investigated the role of EETs in rat isolated perfused kidneys challenged with bolus doses of VitC (Figure 6).…”

“…Although individual EET isomers could not be quantitated by GC/MS analysis, increases in 14,15- trans -EET associated with the inhibition of sEH should play a major role based on the preferred hydrolysis of 14,15- trans -EET by sEH and its potent vasodilator activity in rat renal arcuate arteries [10]. Vasodilator and natriuretic actions of EETs likely contributed to the effects of VitC in the kidney and could provide a direct explanation for the renal protective effects of VitC in reperfusion injuries in renal transplantation [36,37]. Inhibition of EET hydrolysis in the spontaneously hypertensive rat has increased plasma trans -EETs and reduced blood pressure [10].…”

Combating Ischemia-Reperfusion Injury with Micronutrients and Natural Compounds during Solid Organ Transplantation: Data of Clinical Trials and Lessons of Preclinical Findings

“…Vitamin C is a water-soluble vitamin that mainly occurs in fruits and vegetables [91]. Despite acting in a hydrophilic environment, vitamin C can also impact hydrophobic compartments as it acts synergistically with lipophilic vitamin E [250]. Vitamin C possesses direct as well as indirect antioxidative effects.…”

“…The treatment group showed a non-significant trend towards amelioration of inflammation and oxidative stress. In a second study by Norio et al [250] renal cadaveric grafts were treated with 500 mg vitamin C prior to implantation. The authors observed similar results, as the treatment neither affected the incidence on delayed graft function, the rejection rate nor the graft function per se.…”

“…Transplantation [250,253] Intraoperatively [253] treatment of grafts [250] 0.5 mg/mL in 300 ml perfusion solution [250] 500 mg intraoperatively prior to reperfusion [253] anti-inflammatory effects (not statistically significant) [253] anti-oxidative effects (not statistically significant) [253] graft function no effect on delayed graft function [250] no effect on rejection rate [250] no effect on graft function [250] trend towards shorter duration of delayed graft function [250]…”