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.
研究概览
地位
详细说明
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.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Abdulkadir Uçar, MD
- 电话号码：+90 534 030 89 56
- 邮箱：drkadirucar@gmail.com
研究联系人备份
- 姓名：Berna KAYA UĞUR, Doç. Dr.
- 电话号码：+90 532 572 76 51
- 邮箱：bernakayaugur@hotmail.com
学习地点
-
-
State/Province
-
Gaziantep、State/Province、土耳其（türkiye）、27310
- 招聘中
- Gaziantep University Faculty of Medicine Hospital
-
接触：
- Abdulkadir Uçar, MD
- 电话号码：+90 534 030 89 56
- 邮箱：drkadirucar@gmail.com
-
接触：
- Berna KAYA UĞUR, Doç. Dr.
- 电话号码：+90 532 572 76 51
- 邮箱：drkadirucar@gmail.com
-
首席研究员：
- Berna KAYA UĞUR, Doç. Dr.
-
副研究员：
- Abdulkadir Uçar, MD
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：单身的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
有源比较器：Sevoflurane General Anesthesia (SGA)
Participants in this group will receive sevoflurane general anesthesia according to standard institutional protocols for kidney transplantation.
|
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).
其他名称：
|
|
有源比较器：Combined Spinal-Epidural Anesthesia (CSEA)
Participants in this group will receive combined spinal-epidural anesthesia as the anesthetic technique for kidney transplantation.
|
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.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Serum ferroptosis-related biomarkers (Fe, TFRC1, GPX4, MDA, ACSL4) and mitochondrial-derived peptides (humanin and MOTS-c)
大体时间：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)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Delayed Graft Function (DGF)
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
|
合作者和调查者
调查人员
- 首席研究员：Berna KAYA UĞUR, Doç. Dr.、University of Gaziantep
出版物和有用的链接
一般刊物
- 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.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- 2024/420
- 962387 (其他赠款/资助编号：TUBITAK)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.