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2020, Number 1

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Rev Mex Traspl 2020; 9 (1)

Effect of N-acetylcisteine in modulation of oxidative stress, acute kidney injury and immediate graft function in kidney transplant recipients from deceased donors

Escorza-Molina CA, Bobadilla-Sandoval NA, Madrigal-Bustamante JA, Vilatobá-Chapa M, Sánchez-Cedillo IA

Language: Spanish
References: 24
Page: 26-36
PDF size: 320.84 Kb.


ABSTRACT

Ischemia reperfusion injury is constant in kidney transplantation and is associated with cellular damage caused by reactive oxygen species, especially in grafts recovered from deceased donors. N-Acetylcysteine (NAC) is a drug that participates in the neutralization of reactive oxygen species and has proven to be useful in several clinical contexts. The aim of this study was to evaluate biomarkers of oxidative stress, acute kidney injury and immediate function of transplanted kidneys from deceased donors exposed to NAC before clamping during procurement, by measuring biological markers in serum and urine of receptors. Between March 2014 and July 2015, 28 renal grafts were transplanted to adult patients with chronic kidney disease on the waiting list at the Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», whose clinical and surgical protocols were complete; and according to a randomized and blinded procedure with a 1/1 probability, these patients were assigned to receive a donor graft whose management during extraction surgery included systemic intravenous infusion of NAC 30 mg/kg or placebo 2 hours before definitive vascular clamping for extraction. The urinary concentration of NGAL, Hsp72, H2O2 was evaluated at 6, 12 and 24 hours after graft reperfusion and serum MDA at day 7 after transplantation and the occurrence of delayed graft function (DGF) was recorded. There were no complications related to the intervention. There was no difference in the concentrations of biological markers of acute kidney injury and/or oxidative stress between patients with grafts exposed to NAC or placebo; however, in a sub-analysis, patients who presented DGF showed lower urinary concentration of NGAL, Hsp72 and H2O2 when donors received NAC, some of which showed statistical significance (NGAL ng/dL 24 hours post-reperfusion 1056.8 [404.03-2120.17] vs 5891.75 [2197.71-8500.51], NAC vs placebo, p = 0.05; Hsp72 ng/mL 12 hours post-reperfusion 0.39 [0.2-0.52] vs 1.96 [1.17-8.9], NAC vs placebo, p = 0.02; H2O2 nmol/mL 12 hours postreperfusion 5.68 [1.83-7.87] vs 73.32 [51.87-130.87], NAC vs placebo, p = 0.02), suggesting a potential protective effect of the drug on organs subjected to greater ischemic insult by modulating oxidative stress and also revealing lower concentrations of acute kidney injury biomarkers.


REFERENCES

  1. Ditonno P, Impedovo SV, Palazzo S et al. Effects of ischemia-reperfusion injury in kidney transplantation: risk factors and early and long-term outcomes in a single center. Transplant Proc. 2013; 45 (7): 2641-2644. doi: 10.1016/j.transproceed.2013.07.025.

  2. Soares ROS, Losada DM, Jordani MC, Évora P, Castro-E-Silva O. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci. 2019; 20 (20): 5034. doi: 10.3390/ijms20205034.

  3. Arumugam TV, Okun E, Tang SC, Thundyil J, Taylor SM, Woodruff TM. Toll-like receptors in ischemia-reperfusion injury. Shock. 2009; 32 (1): 4-16. doi: 10.1097/SHK.0b013e318193e333.

  4. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013; 1830 (5): 3143-3153. doi: 10.1016/j.bbagen.2012.09.008.

  5. Fixl AN, Woods RM, Dervay K. Intravenous N-acetylcysteine for acetaminophen toxicity. AACN Adv Crit Care. 2017; 28 (4): 305-310. doi: 10.4037/aacnacc2017869.

  6. Wang N, Qian P, Kumar S, Yan TD, Phan K. The effect of N-acetylcysteine on the incidence of contrast-induced kidney injury: a systematic review and trial sequential analysis. Int J Cardiol. 2016; 209: 319-327. doi: 10.1016/j.ijcard.2016.02.083.

  7. D’Amico F, Vitale A, Piovan D et al. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study. Liver Transpl. 2013; 19 (2): 135-144. doi: 10.1002/lt.23527.

  8. Inci I, Erne B, Arni S et al. Prevention of primary graft dysfunction in lung transplantation by N-acetylcysteine after prolonged cold ischemia. J Heart Lung Transplant. 2010; 29 (11): 1293-1301. doi: 10.1016/j.healun.2010.06.017.

  9. Lin A, Sekhon C, Sekhon B et al. Attenuation of ischemia-reperfusion injury in a canine model of autologous renal transplantation. Transplantation. 2004; 78 (5): 654-659. doi: 10.1097/01.tp.0000131664.18670.17.

  10. Orban JC, Quintard H, Cassuto E, Jambou P, Samat-Long C, Ichai C. Effect of N-acetylcysteine pretreatment of deceased organ donors on renal allograft function: a randomized controlled trial. Transplantation. 2015; 99 (4): 746-753. doi: 10.1097/TP.0000000000000395.

  11. Danilovic A, Lucon AM, Srougi M et al. Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation. Transplant Proc. 2011; 43 (5): 1443-1449. doi: 10.1016/j.transproceed.2011.02.020.

  12. Vanmassenhove J, Vanholder R, Nagler E, Van Biesen W. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant. 2013; 28 (2): 254-273. doi: 10.1093/ndt/gfs380.

  13. Sabry A, El-Din AB, El-Hadidy AM, Hassan M. Markers of tubular and glomerular injury in predicting acute renal injury outcome in thermal burn patients: a prospective study. Ren Fail. 2009; 31 (6): 457-463. doi: 10.1080/08860220902963616.

  14. Shoaib M, Mahmud SN, Safdar M. Early diagnosis of acute kidney injury by urinary neutrophil gelatinase associated lipocalin in adult critically ill patients. J Ayub Med Coll Abbottabad. 2019; 31 (1): 12-15.

  15. Li YM, Li Y, Yan L et al. Comparison of urine and blood NGAL for early prediction of delayed graft function in adult kidney transplant recipients: a meta-analysis of observational studies. BMC Nephrol. 2019; 20 (1): 291. doi: 10.1186/s12882-019-1491-y.

  16. Parikh CR, Jani A, Mishra J et al. Urine NGAL and IL-18 are predictive biomarkers for delayed graft function following kidney transplantation. Am J Transplant. 2006; 6 (7): 1639-1645. doi: 10.1111/j.1600-6143.2006.01352.x.

  17. Barrera-Chimal J, Bobadilla NA. Are recently reported biomarkers helpful for early and accurate diagnosis of acute kidney injury? Biomarkers. 2012; 17 (5): 385-393. doi: 10.3109/1354750X.2012.680070.

  18. Ortega-Trejo JA, Pérez-Villalva R, Barrera-Chimal J et al. Heat shock protein 72 (Hsp72) specific induction and temporal stability in urine samples as a reliable biomarker of acute kidney injury (AKI). Biomarkers. 2015; 20 (6-7): 453-459. doi: 10.3109/1354750X.2015.1096305.

  19. Morales-Buenrostro LE, Salas-Nolasco OI, Barrera-Chimal J et al. Hsp72 is a novel biomarker to predict acute kidney injury in critically ill patients. PLoS One. 2014; 9 (10): e109407. doi: 10.1371/journal.pone.01094078

  20. Halliwell B, Clement MV, Long LH. Hydrogen peroxide in the human body. FEBS Lett. 2000; 486 (1): 10-13. doi: 10.1016/s0014-5793(00)02197-9.

  21. Halliwell B, Long LH, Yee TP, Lim S, Kelly R. Establishing biomarkers of oxidative stress: the measurement of hydrogen peroxide in human urine. Curr Med Chem. 2004; 11 (9): 1085-1092. doi: 10.2174/0929867043365404.

  22. Modarresi A, Nafar M, Sahraei Z et al. N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial. Biomarkers. 2018; 23 (6): 589-596. doi: 10.1080/1354750X.2018.1468823.

  23. Kostopanagiotou G, Avgerinos ED, Markidou E et al. Protective effect of NAC preconditioning against ischemia-reperfusion injury in piglet small bowel transplantation: effects on plasma TNF, IL-8, hyaluronic acid, and NO. J Surg Res. 2011; 168 (2): 301-305. doi: 10.1016/j.jss.2009.09.002.

  24. Melih KV, Boynuegri B, Mustafa C, Nilgun A. Incidence, risk factors, and outcomes of delayed graft function in deceased donor kidney transplantation. Transplant Proc. 2019; 51 (4): 1096-1100.




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