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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Abdulkadir Uçar, MD
- Número de teléfono: +90 534 030 89 56
- Correo electrónico: drkadirucar@gmail.com
Copia de seguridad de contactos de estudio
- Nombre: Berna KAYA UĞUR, Doç. Dr.
- Número de teléfono: +90 532 572 76 51
- Correo electrónico: bernakayaugur@hotmail.com
Ubicaciones de estudio
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State/Province
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Gaziantep, State/Province, Turquía (Türkiye), 27310
- Reclutamiento
- Gaziantep University Faculty of Medicine Hospital
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Contacto:
- Abdulkadir Uçar, MD
- Número de teléfono: +90 534 030 89 56
- Correo electrónico: drkadirucar@gmail.com
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Contacto:
- Berna KAYA UĞUR, Doç. Dr.
- Número de teléfono: +90 532 572 76 51
- Correo electrónico: drkadirucar@gmail.com
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Investigador principal:
- Berna KAYA UĞUR, Doç. Dr.
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Sub-Investigador:
- Abdulkadir Uçar, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Único
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: Sevoflurane General Anesthesia (SGA)
Participants in this group will receive sevoflurane general anesthesia according to standard institutional protocols for kidney transplantation.
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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).
Otros nombres:
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Comparador activo: Combined Spinal-Epidural Anesthesia (CSEA)
Participants in this group will receive combined spinal-epidural anesthesia as the anesthetic technique for kidney transplantation.
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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.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Serum ferroptosis-related biomarkers (Fe, TFRC1, GPX4, MDA, ACSL4) and mitochondrial-derived peptides (humanin and MOTS-c)
Periodo de tiempo: Immediately before anesthesia induction and immediately before extubation (intraoperative period)
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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.
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Immediately before anesthesia induction and immediately before extubation (intraoperative period)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Delayed Graft Function (DGF)
Periodo de tiempo: Postoperative days 0-7
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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.
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Postoperative days 0-7
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Postoperative Serum Creatinine Levels
Periodo de tiempo: Postoperative days 1-7
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Serial serum creatinine levels will be measured daily during the first postoperative week to evaluate early renal graft function and recovery.
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Postoperative days 1-7
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Requirement for Postoperative Dialysis
Periodo de tiempo: Within first 7 postoperative days
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The need for dialysis during the early post-transplant period will be recorded as a clinical indicator of graft dysfunction.
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Within first 7 postoperative days
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Urine Output
Periodo de tiempo: Intraoperative period and first 24 postoperative hours
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Hourly urine output will be monitored to assess immediate graft perfusion and early functional recovery.
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Intraoperative period and first 24 postoperative hours
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Length of Hospital Stay
Periodo de tiempo: From surgery until discharge (up to 30 days)
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Total duration of postoperative hospitalization will be recorded as a measure of overall recovery and clinical course.
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From surgery until discharge (up to 30 days)
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Association Between Biomarkers and Clinical Outcomes
Periodo de tiempo: Perioperative period and first 7 postoperative days
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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.
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Perioperative period and first 7 postoperative days
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Berna KAYA UĞUR, Doç. Dr., University of Gaziantep
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- Yong CQY, Tang BL. A Mitochondrial Encoded Messenger at the Nucleus. Cells. 2018 Aug 13;7(8):105. doi: 10.3390/cells7080105.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Procesos Patológicos
- Enfermedades urogenitales masculinas
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Enfermedad crónica
- Atributos de la enfermedad
- Insuficiencia renal
- Insuficiencia Renal Crónica
- Condiciones Patológicas, Signos y Síntomas
- Enfermedades Renales
- Insuficiencia Renal Crónica
- Químicos orgánicos
- Compuestos heterocíclicos
- Compuestos heterocíclicos, anillo fusionado
- Alcaloides
- Hidrocarburos aromáticos policíclicos
- Compuestos policíclicos
- Aniluros
- Amidas
- Compuestos anilina
- Amina
- Compuestos heterocíclicos, 4 o más anillos
- Morfinanos
- Alcaloides opiáceos
- Compuestos heterocíclicos, anillo puente
- Fenantrenos
- Derivados de morfina
- Bupivacaína
- Morfina
Otros números de identificación del estudio
- 2024/420
- 962387 (Otro número de subvención/financiamiento: TUBITAK)
Plan de datos de participantes individuales (IPD)
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Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
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