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

6 juli 2026 bijgewerkt door: Berna Kaya Ugur, University of Gaziantep

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

68

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Turkije (Türkiye)
    • State/Province
      • Gaziantep, State/Province, Turkije (Türkiye), 27310
        • Werving
        • Gaziantep University Faculty of Medicine Hospital
        • Contact:
        • Contact:
        • Hoofdonderzoeker:
          • Berna KAYA UĞUR, Doç. Dr.
        • Onderonderzoeker:
          • Abdulkadir Uçar, MD

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Enkel

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Sevoflurane General Anesthesia (SGA)
Participants in this group will receive sevoflurane general anesthesia according to standard institutional protocols for kidney transplantation.
Geneesmiddel: Sevoflurane General Anesthesia
Participants 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).
Andere namen:
  • Sevoflurane anesthesia
Actieve vergelijker: Combined Spinal-Epidural Anesthesia (CSEA)
Participants in this group will receive combined spinal-epidural anesthesia as the anesthetic technique for kidney transplantation.
Geneesmiddel: Bupivacaine and Morphine for Combined Spinal-Epidural Anesthesia
Participants 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.
Andere namen:
  • CSE anesthesia

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Serum ferroptosis-related biomarkers (Fe, TFRC1, GPX4, MDA, ACSL4) and mitochondrial-derived peptides (humanin and MOTS-c)
Tijdsspanne: Immediately before anesthesia induction and immediately before extubation (intraoperative period)
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.
Immediately before anesthesia induction and immediately before extubation (intraoperative period)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Delayed Graft Function (DGF)
Tijdsspanne: Postoperative days 0-7
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 days 0-7
Postoperative Serum Creatinine Levels
Tijdsspanne: Postoperative days 1-7
Serial serum creatinine levels will be measured daily during the first postoperative week to evaluate early renal graft function and recovery.
Postoperative days 1-7
Requirement for Postoperative Dialysis
Tijdsspanne: Within first 7 postoperative days
The need for dialysis during the early post-transplant period will be recorded as a clinical indicator of graft dysfunction.
Within first 7 postoperative days
Urine Output
Tijdsspanne: Intraoperative period and first 24 postoperative hours
Hourly urine output will be monitored to assess immediate graft perfusion and early functional recovery.
Intraoperative period and first 24 postoperative hours
Length of Hospital Stay
Tijdsspanne: From surgery until discharge (up to 30 days)
Total duration of postoperative hospitalization will be recorded as a measure of overall recovery and clinical course.
From surgery until discharge (up to 30 days)
Association Between Biomarkers and Clinical Outcomes
Tijdsspanne: Perioperative period and first 7 postoperative days
Correlation analyses will be performed to evaluate the relationship between perioperative biomarker levels (ferroptosis markers, humanin, and MOTS-c) and early clinical outcomes, including delayed graft function, serum creatinine levels, and urine output.
Perioperative period and first 7 postoperative days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of Gaziantep

Medewerkers

The Scientific and Technological Research Council of Turkey

Onderzoekers

  • Hoofdonderzoeker: Berna KAYA UĞUR, Doç. Dr., University of Gaziantep

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 maart 2026

Primaire voltooiing (Geschat)

1 oktober 2026

Studie voltooiing (Geschat)

15 oktober 2026

Studieregistratiedata

Eerst ingediend

24 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

24 juni 2026

Eerst geplaatst (Werkelijk)

1 juli 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

8 juli 2026

Laatste update ingediend die voldeed aan QC-criteria

6 juli 2026

Laatst geverifieerd

1 juli 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 2024/420
  • 962387 (Ander subsidie-/financieringsnummer: TUBITAK)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

Individual participant data will not be publicly shared. Data may be available from the corresponding investigator upon reasonable request and after approval by the local ethics committee.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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