Renal transplantation is the most effective renal replacement therapy for patients with end-stage renal disease. Ischemia-reperfusion injury may adversely affect graft function and long-term outcomes. Ferroptosis has recently emerged as a potential mechanism involved in ischemia-reperfusion injury, while the mitochondrial-derived peptides humanin and MOTS-c are thought to exert protective effects against oxidative stress. However, the effects of different anesthetic techniques on these biomarkers in kidney transplant recipients have not been investigated.
This prospective controlled study aims to compare the effects of sevoflurane general anesthesia (SGA) and combined spinal-epidural anesthesia (CSEA) on serum ferroptosis markers, humanin, and MOTS-c levels in adult kidney transplant recipients. Blood samples will be obtained perioperatively for biomarker analysis.
The primary objective of the study is to evaluate the effects of the anesthetic technique on serum ferroptosis markers, humanin, and MOTS-c levels. Secondary objectives include evaluating early graft function and postoperative outcomes by assessing the incidence of delayed graft function, postoperative serum creatinine levels, requirement for dialysis, urine output, length of hospital stay, and the association of these outcomes with perioperative biomarker levels.
Patients aged 18-70 years with American Society of Anesthesiologists (ASA) physical status I-III.
Patients scheduled for elective living-donor allogeneic kidney transplantation.
Patients receiving sevoflurane-based general anesthesia as the anesthetic technique.
Patients receiving combined spinal-epidural anesthesia as the anesthetic technique.
Patients younger than 18 years or older than 70 years.
Patients undergoing deceased-donor kidney transplantation.
Patients receiving total intravenous anesthesia (TIVA).
Patients who decline to participate in the study or are unable to provide informed consent.
Parallel
Sevoflurane General Anesthesia
DrugParticipants will receive standardized sevoflurane general anesthesia according to institutional kidney transplantation protocols. Anesthesia induction will include preoxygenation with 100% oxygen for 3-5 minutes, followed by intravenous propofol (1.5-2.5 mg/kg), fentanyl (1-2 µg/kg), and rocuronium bromide (0.6 mg/kg). Endotracheal intubation will be performed after short mask ventilation using direct laryngoscopy, and correct placement will be confirmed by auscultation. Anesthesia maintenance will be provided with sevoflurane (1.5-2.0% end-tidal) in a 40-50% oxygen/air mixture and remifentanil infusion (0.05-0.2 µg/kg/min). Mechanical ventilation will be set to 6-8 mL/kg tidal volume, PEEP 5 cmH₂O, and end-tidal CO₂ 35-40 mmHg. At the end of surgery, sevoflurane will be discontinued, neuromuscular blockade will be reversed with sugammadex (2-4 mg/kg), and extubation will be performed after recovery. Postoperative analgesia will include subcutaneous morphine (0.1 mg/kg).
Bupivacaine and Morphine for Combined Spinal-Epidural Anesthesia
DrugParticipants will receive combined spinal-epidural anesthesia under sterile conditions according to institutional protocols. The L3-L4 interspace will be identified, and local anesthesia will be administered with lidocaine (2-3 mL, 2%). A Tuohy needle will be inserted using a midline approach, and the epidural space will be identified using loss-of-resistance technique. Spinal anesthesia will be achieved via intrathecal injection of 2.5 mL of 0.5% hyperbaric bupivacaine after confirmation of cerebrospinal fluid flow. An epidural catheter will then be placed and secured. Sedation will be provided with intravenous midazolam (1-2 mg), and oxygen will be administered via nasal cannula (4 L/min). Intraoperative analgesia will be maintained with epidural 0.25% bupivacaine as needed. At the end of surgery, epidural morphine (3 mg) combined with 0.25% bupivacaine will be administered for postoperative analgesia.
Serum ferroptosis-related biomarkers (Fe, TFRC1, GPX4, MDA, ACSL4) and mitochondrial-derived peptides (humanin and MOTS-c)
The primary outcome is the perioperative change in serum levels of ferroptosis-related biomarkers and mitochondrial-derived peptides, including humanin and MOTS-c, between two standardized time points. Blood samples will be collected immediately prior to anesthesia induction and immediately prior to extubation. Biomarker levels will be quantified using ELISA-based and standard biochemical methods. The primary comparison will evaluate differences in biomarker changes between the sevoflurane general anesthesia (SGA) and combined spinal-epidural anesthesia (CSEA) groups.
Delayed Graft Function (DGF)
Delayed graft function will be defined as the requirement for dialysis within the first 7 postoperative days or a reduction in serum creatinine of less than 30% during the first 48 hours after transplantation. The incidence of delayed graft function will be compared between the study groups.
Postoperative Serum Creatinine Levels
Serial serum creatinine levels will be measured daily during the first postoperative week to evaluate early renal graft function and recovery.
Requirement for Postoperative Dialysis
The need for dialysis during the early post-transplant period will be recorded as a clinical indicator of graft dysfunction.
Urine Output
Hourly urine output will be monitored to assess immediate graft perfusion and early functional recovery.
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University of Gaziantep
Lead sponsor
The Scientific and Technological Research Council of Turkey
Collaborator
