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Short-Time Intermittent Preexposure of Living Human Donors To Hindawi Publishing Corporation Journal of Transplantation Volume 2011, Article ID 204843, 8 pages doi:10.1155/2011/204843 Clinical Study Short-Time Intermittent Preexposure of Living Human Donors to Hyperoxia Improves Renal Function in Early Posttransplant Period: A Double-Blind Randomized Clinical Trial Kamran Montazeri,1 Mohammadali Vakily,1 Azim Honarmand,1 Parviz Kashefi,1 Mohammadreza Safavi,1 Shahram Taheri,2 and Bahram Rasoulian3 1 Anesthesiology and Critical Care Research Center, Isfahan University of Medical Sciences, P.O. Box 8174675731, Isfahan 81744, Iran 2 Isfahan Kidney Diseases Research Center (IKRC) and Internal Medicine Department, Alzahra Hospital, Isfahan University of Medical Sciences, P.O. Box 8174675731, Isfahan 81744, Iran 3 Research Center and Department of Physiology, Lorestan University of Medical Sciences, P.O. Box 6814617767, Khorramabad, Iran Correspondence should be addressed to Azim Honarmand, [email protected] Received 6 November 2010; Revised 5 January 2011; Accepted 26 January 2011 Academic Editor: Wojciech A. Rowinski´ Copyright © 2011 Kamran Montazeri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The purpose of this human study was to investigate the effect of oxygen pretreatment in living kidney donors on early renal function of transplanted kidney. Sixty living kidney donor individuals were assigned to receive either 8–10 L/min oxygen (Group I) by a non-rebreather mask with reservoir bag intermittently for one hour at four times (20, 16, 12, and 1 hours before transplantation) or air (Group II). After kidney transplantation, urine output, blood urea nitrogen (BUN), serum creatinine, need to additional diuretics (NTADs) in the first 24 hours after transplantation, delayed graft function (DGF), the creatinine clearance (CrCL) on 10th day, and duration of hospital stay from the first posttransplant day till normalization of renal function was recorded and compared in two groups. Mean CrCL in posttransplant day 10, NTAD after 24 hours of transplantation, and urine output during 6 hours after operation were significantly better in Group I compared with Group II (P<.05). Also, DGF during the first week after operation and duration of hospital stay was less in Group I compared with Group II. Intermittent exposure of human living kidney donor to hyperoxic environment may improve renal function following kidney transplantation. 1. Introduction Delayed graft function (DGF) was defined as hemodial- ysis requirement during the first week after renal transplan- Preservation of renal function is an essential purpose tation. Reperfusion injury is a risk factor for development of in renal transplantation and in many other vascular and DGF after transplantation [7]. urological procedures where renal functional impairment Therefore, protective maneuvers before transplantation follows ischemia-reperfusion (I-R) injury [1]. Ischemic could obviously profit the fate of the organ. Murry et al. injury occurs when the blood supply to a tissue is inter- [8] in 1986 demonstrated that the application of short- rupted, but paradoxically more severe tissue injury arises time episodes of ischemia and reperfusion to the dog’s when blood flow is restored on reperfusion [2]. Renal myocardium led to the development of tolerance to subse- warm I-R injury happens during kidney transplantation and quent more prolonged ischemia and reperfusion and imple- hasamajorimpactonmorbidity[3], on cost increase [4], ment the term “ischemic preconditioning” (IPC) to express and on prognosis [5, 6]. this endogenous inducible protection. This phenomenon has 2 Journal of Transplantation been primarily investigated and characterized in the heart In the first five donors in each group, an arterial blood [9, 10], but it has also been explained in the liver [11], the gas (ABG) test was done with permission of the participants small intestine [12], lung [13], brain [14], and kidney [15]. for measuring the oxygen arterial partial pressure (PaO2)and Inducing brief episodes of ischemia and reperfusion in assessing the effectiveness of oxygen administration. human appears fairly aggressive and not satisfactory by Recipients and their medical team were blinded to many surgeons [16]. Accordingly finding safer methods of the study group assignments. Before transplant operation, preconditioning against IR injury is crucial. all recipients received 500 mg IV methylprednisolone, 6– Amongst the most practical methods for induction of 8 mg/kg cyclosporine A, and 1 gram mycophenolate mofetil. ischemic tolerance in tissues is short-period exposure to Data concerned recipients (age, weight, gender, primary hyperoxia which has no significant adverse effects and renal disease, time on dialysis, urinary output status (oliguric occasionally appears to be beneficial (e.g., by maximizing or anuric), type of dialysis, serology to hepatitis C and arterial oxygen saturation). In animal models, the protective B virus, and last panel-reactive antibodies), and donors effects of oxygen pretreatment on subsequent ischemia- (age, gender, and serology to hepatitis C and B virus) were reperfusion injury have been confirmed in heart [17, 18], recorded in both groups. brain [19], spinal cord [20], and finally kidney [21, 22]. No anesthetic premedication was given to the recipients Wahhabaghai and colleagues [22] showed that repeated and donors. Peripheral oxygen saturation (SpO2), electro- exposure to hyperoxic (≥95% O2)environmentcandecrease cardiogram, noninvasive arterial blood pressure, and heart rat’s renal ischemia-reperfusion damage. rate were recorded in the operating room. After 3–5 minutes Since free radical formation is the main cause of IR injury preoxygenation with 100% oxygen, anesthesia was induced [1], the mechanism of hyperoxia-induced preconditioning with thiopental 5 mg/kg and fentanyl 3 μg/kg followed against IR injury appears to be induction of endogenous by atracurium 0.6 mg/kg to facilitate tracheal intubation. defense strategies against free radicals by low grade oxidative Anaesthesia was maintained with isoflurane 1–1.2% and stress resulting from short period of exposure to hyperoxia nitrous oxide 50% in oxygen, and patients were maintained [18]. under controlled ventilation to achieve end-tidal CO2 values To the best of our knowledge, there is no human study of 32–35 mmHg. which indicates this effect of oxygen pretreatment on renal In recipients, fentanyl 1 μg/kg was given as rescue med- function of transplanted kidney. Therefore, the present study ication when insufficient analgesia was noted (defined as a was undertaken to determine whether brief exposure to the heart rate or systolic arterial blood pressure that exceeded hyperoxia in living donors could improve renal function baseline values by 20%). All recipients received normal saline measured throughout 10 days after kidney transplantation. 0.9% 70 mL/kg and furosemide 3 mg/kg before completion of vascular anastomosis. Residual neuromuscular blockade was reversed by neostigmine 40 μg/kg and atropine 20 μg/ kg 2. Material and Methods at the end of surgery. After emergence from anaesthesia, patients were cared From October 2007 to December 2009, sixty ASA (American in the postanaesthetic care unit (PACU). They received society of Anesthesiology) III patients with end-stage renal supplemental O2 at a rate of 2–4 L/min with nasal prongs and disease who had undergone first kidney transplant from were transferred to the kidney transplant intensive care unit a living donor, aged 18–65 years old, with no history of after stabilization. previous transplantation, human immunodeficiency, and In donors, induction and maintenance of anesthesia hepatitis B and C virus infection were recruited to participate were similar and so for recipient patients. In donors, in this randomized, double blind clinical trial study. patients received 30 mL/kg Ringer until just before open The kidney donors were 18–55 years old healthy (ASA nephrectomy. After nephrectomy, the kidney was prepared in I) individuals who were evaluated for kidney donation by University of Wisconsin (UW) solution at 4◦Ctemperature corresponding nephrologists and their own recipients were and immediately transplanted to recipients. WBC cross match negative. After kidney transplantation, urine output was moni- The study protocol was approved by the medical ethics tored closely for volume hourly for the first 24 hours and research committee of our university, and written informed recorded for statistical analysis during 1, 6, and 24 hours. If consent was obtained from each kidney donor. the patients had urine output volume less than 200 mL per Recipients with new onset of any major complications hour in spite of adequate fluid therapy, additional diuretics (myocardial infarction, stroke, hemorrhagic shock, etc.) (furosemide 10 mg per hour) were administered. Also, blood after transplantation, female donors to male recipients, and urea nitrogen (BUN) and serum creatinine (sCr), serum donors who were noncompliant with study protocol and sodium and potassium were tested and recorded daily for received maintenance anesthesia other than isoflurane were 10 days. excluded from the study. Urine sodium and creatinine were measured, and the At enrolment, living kidney donors were assigned by a fractional excretion of sodium (FENa) was calculated on the computer-generated list of random numbers to receive either
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