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

NCT07678073 | Recruiting

• 2 other identifiers: 2024/420962387
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Disease, End-Stage; Kidney Transplant; Kidney; Kidney Disease; Renal Transplant

Keywords

GENERAL ANESTHESIA; REGIONAL ANESTHESIA; KIDNEY TRANSPLANTATION; CELLULAR STRESS RESPONSE; CELLULAR STRESS; ANESTHESIA; HUMANIN; MOTS-c; FERROPTOSIS

Outcome Measures

Primary Outcomes (1)

• 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.

  Immediately before anesthesia induction and immediately before extubation (intraoperative period)

Secondary Outcomes (6)

• Delayed Graft Function (DGF)

  Postoperative days 0-7

• Postoperative Serum Creatinine Levels

  Postoperative days 1-7

• Requirement for Postoperative Dialysis

  Within first 7 postoperative days

• Urine Output

  Intraoperative period and first 24 postoperative hours

• Length of Hospital Stay

  From surgery until discharge (up to 30 days)

Study Arms (2)

Sevoflurane General Anesthesia (SGA)

ACTIVE COMPARATOR

Participants in this group will receive sevoflurane general anesthesia according to standard institutional protocols for kidney transplantation.

Drug: Sevoflurane General Anesthesia

Combined Spinal-Epidural Anesthesia (CSEA)

ACTIVE COMPARATOR

Participants in this group will receive combined spinal-epidural anesthesia as the anesthetic technique for kidney transplantation.

Drug: Bupivacaine and Morphine for Combined Spinal-Epidural Anesthesia

Interventions

Sevoflurane General Anesthesia DRUG

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).

Also known as: Sevoflurane anesthesia

Sevoflurane General Anesthesia (SGA)

Bupivacaine and Morphine for Combined Spinal-Epidural Anesthesia DRUG

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.

Also known as: CSE anesthesia

Combined Spinal-Epidural Anesthesia (CSEA)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Gaziantep: lead
• The Scientific and Technological Research Council of Turkey: collaborator

Study Sites (1)

Gaziantep University Faculty of Medicine Hospital

Gaziantep, State/Province, 27310, Turkey (Türkiye)

RECRUITING

Related Publications (13)

• Ivascu R, Torsin LI, Hostiuc L, Nitipir C, Corneci D, Dutu M. The Surgical Stress Response and Anesthesia: A Narrative Review. J Clin Med. 2024 May 20;13(10):3017. doi: 10.3390/jcm13103017.

  PMID: 38792558 BACKGROUND

• Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011 Nov;11(11):2279-96. doi: 10.1111/j.1600-6143.2011.03754.x. Epub 2011 Sep 19.

  PMID: 21929642 BACKGROUND

• Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004 Nov 13-19;364(9447):1814-27. doi: 10.1016/S0140-6736(04)17406-0.

  PMID: 15541456 BACKGROUND

• Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023 Jan 25;14:1120533. doi: 10.3389/fendo.2023.1120533. eCollection 2023.

  PMID: 36761202 BACKGROUND

• Yong CQY, Tang BL. A Mitochondrial Encoded Messenger at the Nucleus. Cells. 2018 Aug 13;7(8):105. doi: 10.3390/cells7080105.

  PMID: 30104535 BACKGROUND

• Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023 Jan 20;21(1):36. doi: 10.1186/s12967-023-03885-2.

  PMID: 36670507 BACKGROUND

• Coradduzza D, Congiargiu A, Chen Z, Cruciani S, Zinellu A, Carru C, Medici S. Humanin and Its Pathophysiological Roles in Aging: A Systematic Review. Biology (Basel). 2023 Apr 6;12(4):558. doi: 10.3390/biology12040558.

  PMID: 37106758 BACKGROUND

• Gong Z, Tas E, Muzumdar R. Humanin and age-related diseases: a new link? Front Endocrinol (Lausanne). 2014 Dec 4;5:210. doi: 10.3389/fendo.2014.00210. eCollection 2014.

  PMID: 25538685 BACKGROUND

• Gong Z, Goetzman E, Muzumdar RH. Cardio-protective role of Humanin in myocardial ischemia-reperfusion. Biochim Biophys Acta Gen Subj. 2022 Feb;1866(2):130066. doi: 10.1016/j.bbagen.2021.130066. Epub 2021 Dec 9.

  PMID: 34896254 BACKGROUND

• Hazafa A, Batool A, Ahmad S, Amjad M, Chaudhry SN, Asad J, Ghuman HF, Khan HM, Naeem M, Ghani U. Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases. Life Sci. 2021 Jan 1;264:118679. doi: 10.1016/j.lfs.2020.118679. Epub 2020 Oct 29.

  PMID: 33130077 BACKGROUND

• Wang W, Chen J, Zhan L, Zou H, Wang L, Guo M, Gao H, Xu J, Wu W. Iron and ferroptosis in kidney disease: molecular and metabolic mechanisms. Front Immunol. 2025 Feb 5;16:1531577. doi: 10.3389/fimmu.2025.1531577. eCollection 2025.

  PMID: 39975561 BACKGROUND

• Feng Q, Yu X, Qiao Y, Pan S, Wang R, Zheng B, Wang H, Ren KD, Liu H, Yang Y. Ferroptosis and Acute Kidney Injury (AKI): Molecular Mechanisms and Therapeutic Potentials. Front Pharmacol. 2022 Apr 19;13:858676. doi: 10.3389/fphar.2022.858676. eCollection 2022.

  PMID: 35517803 BACKGROUND

• Liu J, Han X, Zhou J, Leng Y. Molecular Mechanisms of Ferroptosis and Their Involvement in Acute Kidney Injury. J Inflamm Res. 2023 Nov 2;16:4941-4951. doi: 10.2147/JIR.S427505. eCollection 2023.

  PMID: 37936596 BACKGROUND

Related Links

• The provided link refers to the official website of Gaziantep University Faculty of Medicine Hospital, where the study will be conducted and institutional information can be accessed.

MeSH Terms

Conditions

Kidney Failure, Chronic; Kidney Diseases

Interventions

Bupivacaine; Morphine

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Berna KAYA UĞUR, Doç. Dr.

  University of Gaziantep

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abdulkadir UÇAR, MD

CONTACT

+90 534 030 89 56; drkadirucar@gmail.com

Berna KAYA UĞUR, Doç. Dr.

CONTACT

+90 532 572 76 51; bernakayaugur@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Laboratory personnel performing sample processing and biomarker analysis will be blinded to group allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: The study will use a parallel assignment interventional model. Participants will be assigned to one of two study groups: sevoflurane general anesthesia (SGA) or combined spinal-epidural anesthesia (CSEA). Outcomes will be compared between the two groups to evaluate the effect of anesthetic technique on perioperative biomarker levels and clinical outcomes.

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: July 1, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 15, 2026
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)