Evaluation of the effect of high dose intravenous vitamin C on delayed allograft function in deceased donor kidney transplantation: a preliminary report

Abstract

Background: Delayed graft function (DGF) can affect short-and long-term allograft outcomes in kidney transplant recipients. One of the pathophysiological pathways in the occurrence of DGF is ischemia-reperfusion injury (IRI). High dose intravenous vitamin C has proven efficacy in decreasing IRI consequences. Accordingly, we designed this study to assess the effect of high dose intravenous vitamin C on the incidence and duration of DGF. Methods: This is a pilot, single-center, double-blinded, randomized, placebo-controlled trial. In the treatment group, kidney transplant recipients received vitamin C infusion at the dose of 70 mg/kg diluted in 0.45% saline, and in another study arm, only the diluent solution was administered. Data regarding allograft function and other clinical information was recorded. Results: This preliminary study on 19 patients (9 cases in the vitamin C and 10 cases in the placebo group) showed that after administration of single, high dose vitamin C the incidence of DGF was not significantly different between the groups, but the duration of DGF was substantially shorter in the vitamin C group than the placebo group (7.33 ± 5.68 versus 19.66 ± 0.57 days; P = 0.02). Acute rejection episodes were more seen in the vitamin C group than in the placebo group. Although this data was not statistically significant (P = 0.37), it led to the termination of the study. Conclusion: A high dose of intravenous vitamin C before allograft implantation was effective in decreasing DGF duration but not DGF incidence. Trial registration: The trial was registered in the Iranian registry of clinical trials encoded IRCT20100111003043N13 on June 24, 2019.

Progress and Setbacks in Translating a Decade of Ferroptosis Research into Clinical Practice

“…In the corresponding mouse model of renal IRI, ferroptosis inhibitors are typically administered shortly before IRI induction [ 28 ], a fact that is important to acknowledge, as such a preventative strategy requires control over the timing of damage induction. While the protective effects of ferroptosis inhibition in renal IRI are reproducible [ 60 , 68 , 69 , 70 ], clinically, neither a small trial evaluating vitamin C [ 71 ] nor a large randomized controlled trial (RCT) evaluating NAC in human kidney transplantation demonstrated benefit in terms of DGF incidence [ 72 ]. Thus far, efforts to prevent IRI in kidney transplantation have focused on mechanical solutions such as bridging cold ischemia time with artificial machine perfusion, successfully reducing DGF risk by ≥50% [ 73 , 74 ].…”

Efficacy and safety of perioperative vitamin C in patients undergoing noncardiac surgery: a systematic review and meta-analysis of randomised trials

“…2). 29,30,35,50,51,54,57 Nine trials (n¼478) did not report any outcome of interest for the present systematic review, so the risk of bias judgement was not performed (Supplementary Table 3). 25,32,36,38e40,47 Fifteen trials reported details on authors' conflict of interests and funding sources, and no major concerns were found (Supplementary Table 4).…”

“…34 Concerns on vitamin C safety were raised by one doubleblinded placebo-controlled trial performed in 20 patients undergoing kidney transplantation, and receiving a single 70 mg kg À1 intravenous dose of vitamin C within 1 h of transplantation. 57 One patient was withdrawn because of shortness of breath and fatigue after infusion of one-third of ascorbate solution. The study was terminated early owing to safety concerns as acute rejection was observed in six of nine patients in the vitamin C group and four of 10 in the placebo group (P¼0.37 according to the study).…”

“…Furthermore, safety and adverse events definitions were heterogenous or lacking. Borran and colleagues 57 published results of a trial that was terminated early because of safety concerns since acute rejection after kidney transplantation (six of nine patients vs four of 10, P¼0.37). Notably, the difference between the two groups was not significant, and the study was small and not powered for this outcome, increasing the risk of type I error (false positive).…”