Effect of N-acetylcysteine pretreatment of deceased organ donors on renal allograft function: a randomized controlled trial

Jean-Christophe Orban, Hervé Quintard, Elisabeth Cassuto, Patrick Jambou, Corine Samat-Long, Carole Ichai, Jean-Christophe Orban, Hervé Quintard, Elisabeth Cassuto, Patrick Jambou, Corine Samat-Long, Carole Ichai

Abstract

Background: Antioxidant donor pretreatment is one of the pharmacologic strategy proposed to prevent renal ischemia-reperfusion injuries and delayed graft function (DGF). The aim of the study was to investigate whether a donor pretreatment with N-acetylcysteine (NAC) reduces the incidence of DGF in adult human kidney transplant recipients.

Methods: In this randomized, open-label, monocenter trial, 160 deceased heart-beating donors were allowed to perform 236 renal transplantations from September 2005 to December 2010. Donors were randomized to receive, in a single-blind controlled fashion, 600 mg of intravenous NAC 1 hr before and 2 hr after cerebral angiography performed to confirm brain death. Primary endpoint was DGF defined by the need for at least one dialysis session within the first week or a serum creatinine level greater than 200 μmol/L at day 7 after kidney transplantation.

Results: The incidence of DGF was similar between donors pretreated with or without NAC (39/118; 33% vs. 30/118; 25.4%; P = 0.19). Requirement for at least one dialysis session was not different between the NAC and No NAC groups (17/118; 14.4% vs. 14/118; 11.8%, P = 0.56). The two groups had comparable serum creatinine levels, estimated glomerular filtration rates, and daily urine output at days 1, 7, 15, and 30 after kidney transplantation as well as at hospital discharge. No difference in recipient mortality nor in 1-year kidney graft survival was observed.

Conclusion: Donor pretreatment with NAC does not improve delayed graft function after kidney transplantation.

Trial registration: ClinicalTrials.gov NCT00998972.

Conflict of interest statement

The authors declare no funding and conflicts of interest.

clinicaltrials.gov.identifier NCT 00998972

Figures

FIGURE 1
FIGURE 1
Flow diagram for study enrollment and randomization of donors and recipients.
FIGURE 2
FIGURE 2
Time course of serum creatinine (A), eGFR (B) in the first month after renal transplantation assessed at days 1, 7, 14, and 30. Data markers represent the mean and the error bars, SD. Numbers of values at days 7, 14, and 30 were smaller than the number of recipients because of missing data and of patients discharged from hospital. A, The two-way analysis for repeated measurements showed that the factor time was significant (P < 0.0001), whereas both the factor group and the interaction between group and time were not significant (respectively, P = 0.653 and P = 0.472). *P < .0001 day 1 vs. days 7, 14, and 30 in both groups (post hoc analysis F Scheffe test). B, eGFR was calculated using the MDRD formula. The two-way analysis for repeated measurements showed that the factor time was significant (P < 0.0001), whereas both the factor group and the interaction between group and time were not significant (respectively P = 0.826 and P = 0.531). MDRD, Modification of the Diet in Renal Disease; eGRF, estimated glomerular filtration rate; SD, standard deviation.
FIGURE 3
FIGURE 3
Time course of daily urine production in the first month after renal transplantation assessed at days 1, 7, 14, and 30. * P < 0.0001 day 1 vs. days 7, 14, and 30 in both groups (post hoc analysis F Scheffe test). C, The two-way analysis for repeated measurements showed that the factor time and the factor group were not significant (respectively P = 0.820 and P = 0.172).

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