Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation

Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation: A Prospective Controlled Study

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.

Renal transplantation represents the most effective form of renal replacement therapy for patients with end-stage renal disease; however, ischemia-reperfusion injury remains a major determinant of early graft dysfunction and long-term transplant outcomes.

Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, has recently been proposed as an important mechanism contributing to ischemia-reperfusion-related tissue injury. In addition, mitochondrial-derived peptides such as humanin and MOTS-c have been identified as key regulators of cellular stress responses and may exert protective effects against oxidative damage. Despite these emerging findings, the influence of anesthetic technique on ferroptosis-related pathways and mitochondrial protective peptides in kidney transplantation has not yet been fully elucidated.

This prospective controlled study is designed to evaluate the effect of anesthetic technique on perioperative biochemical and clinical outcomes in renal transplant recipients. Adult patients undergoing kidney transplantation will receive either sevoflurane-based general anesthesia (SGA) or combined spinal-epidural anesthesia (CSEA). The two anesthetic strategies will be compared in terms of their effects on circulating ferroptosis-related biomarkers, as well as serum levels of humanin and MOTS-c.

Peripheral arterial blood samples will be obtained at two standardized points: immediately before anesthesia induction (T1) and immediately prior to extubation (T2). Following collection, blood samples will be centrifuged, and serum aliquots will be stored under appropriate conditions at -80°C until batch analysis. Serum levels of ferroptosis-related biomarkers, humanin, and MOTS-c will be measured using enzyme-linked immunosorbent assay (ELISA) and standard biochemical techniques.

The primary objective of the study is to assess the effect of anesthetic technique on perioperative changes in serum ferroptosis-related biomarkers and mitochondrial-derived peptides (humanin and MOTS-c).

The secondary objectives are to evaluate early postoperative graft function and clinical recovery parameters, including incidence of delayed graft function, postoperative serum creatinine levels, requirement for dialysis, urine output, and length of hospital stay. In addition, the association between perioperative biomarker levels and clinical outcomes will be analyzed to explore potential predictive relationships.

It is anticipated that this study will provide further insight into the relationship between anesthetic technique, ferroptosis pathways, and mitochondrial-mediated cytoprotection in renal transplantation. The results may contribute to improved understanding of perioperative biological responses and support optimization of anesthetic strategies aimed at enhancing graft outcomes.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Patients with American Society of Anesthesiologists (ASA) physical status IV or V.
• Patients with a history of previous organ transplantation.
• Patients with known or suspected mitochondrial disorders.
• Patients with a history of chronic corticosteroid use.
• Patients requiring red blood cell transfusion intraoperatively or within the first 24 postoperative hours.
• Patients with a primary warm ischemia time >5 minutes, secondary warm ischemia time >30 minutes, or cold ischemia time >60 minutes.