Effects Of Propofol And Sevoflurane On Plasma Mirna Levels İn Living Kidney Donors

NCT07760402 | Recruiting

• 1 other identifier: 2024-KAEK-39
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Surgical interventions and associated tissue trauma induce a complex systemic inflammatory stress response characterized by the activation of neuroendocrine, metabolic, and immunological systems. Donor nephrectomy operations performed in living kidney donors are among the unique clinical models where these inflammatory cascades and cellular stress pathways are most intensely observed, due to major surgical trauma and unavoidable ischemia-reperfusion injury during organ clamping. Recent studies have demonstrated that microRNAs (miRNAs), which epigenetically regulate gene expression at the post-transcriptional level, serve as key determinants in perioperative medicine regarding immune response, resolution of inflammation, and cellular adaptation processes . Among our target molecules, miR-146a acts as a dominant, negative regulator (brake mechanism) of the innate immune response , while miR-155 plays an important role in the inflammatory response by triggering pro-inflammatory macrophage activation . Conversely, miR-21 displays an anti-apoptotic adaptation mechanism against tissue damage by directly targeting programmed cell death pathways . Propofol, an intravenous agent, and sevoflurane, a volatile anesthetic, are known to differentially impact microRNAs in circulating extracellular vesicles during major surgical interventions . The original value of this study lies in being the first randomized clinical trial in the literature to comprehensively examine the acute comparative effects of these two anesthesia techniques on perioperative inflammatory miRNA expression profiles in completely healthy living kidney donors. The objective is to comparatively evaluate the dynamic changes in plasma miR-146a, miR-155, and miR-21 levels under general anesthesia maintained with propofol or sevoflurane. Regarding the methodology, the research will be conducted on 34 voluntary living kidney donors aged 18-65 in the ASA I-II risk group, scheduled for elective donor nephrectomy at Gaziantep University Faculty of Medicine Şahinbey Training and Research Hospital, Department of Anesthesiology and Reanimation. Donors will be allocated into two equal groups (Group P: Propofol, n=17 and Group S: Sevoflurane, n=17) using a computer-assisted block randomization method, with anesthesia maintenance titrated to a Bispectral Index (BIS) of 40-60. Peripheral venous blood samples will be collected into K3-EDTA tubes at three different time points: before anesthesia induction (T0: basal), at the end of surgery (T1), and at the postoperative 24th hour (T2). In accordance with project management and data privacy principles, personal identity information will be masked, and each participant will be recorded in the system with a unique "File Number" (Dosya No). In the molecular phase conducted in coordination with the Department of Medical Genetics laboratory, total RNA isolation and cDNA synthesis will be performed from plasma samples separated under cold chain rules. Expression levels of target genes and the U6 snRNA internal control will be quantitatively analyzed in duplicate using Real-Time Quantitative PCR (RT-qPCR). Fold change ratios will be calculated using the method and analyzed with biostatistical methods including Shapiro-Wilk, Student's t-test, and Mann-Whitney U test. As for the widespread impact, the molecular findings to be obtained will elucidate the epigenetic reflections of general anesthesia applications on systemic inflammation and organ protection capacities for the first time. These results will lead to the development of the safest, evidence-based anesthesia protocols that will minimize the inflammatory load caused by surgical trauma at the cellular level in living kidney donors, increase donor comfort and postoperative recovery quality, and protect kidney graft quality against ischemic injury, providing a strong scientific foundation for international transplantation guidelines.

Conditions

Kidney Transplant

Keywords

Living donor; microRNAs; sevoflurane; propofol

Outcome Measures

Primary Outcomes (1)

• Relative expression levels of plasma microRNAs (miR-146a, miR-155, and miR-21)

  The relative changes in the expression levels of plasma miR-146a, miR-155, and miR-21 will be evaluated using blood samples. Total RNA will be isolated from serum samples using commercial kits, followed by complementary DNA (cDNA) synthesis and Quantitative Real-Time PCR (RT-PCR) array analysis. The 2\^-ΔΔCt method will be utilized to calculate relative gene expression folds, using U6 as an internal control reference gene.

  Baseline (pre-induction), immediately at the end of surgery (post-extubation), and at the 24th postoperative hour.

Study Arms (2)

GROUP S

ACTIVE COMPARATOR

General anesthesia maintenance will be provided using Sevoflurane at a concentration of 1.5-2% combined with a 50% Air / 50% Oxygen mixture. Standard monitoring and routine anesthesia induction protocols will be implemented.

Drug: Sevoflurane

GROUP P

ACTIVE COMPARATOR

General anesthesia maintenance will be provided using Total Intravenous Anesthesia (TIVA) via Propofol infusion at a dose of 4-10 mg/kg/hour combined with a 50% Air / 50% Oxygen mixture. Standard monitoring and routine anesthesia induction protocols will be implemented.

Drug: propofol

Interventions

Sevoflurane DRUG

Inhalation anesthetic agent administered at a concentration of 1.5-2% with a 50% Air / 50% Oxygen mixture for the maintenance of general anesthesia.

GROUP S

propofol DRUG

Intravenous anesthetic agent administered via continuous TIVA infusion at a dose of 4-10 mg/kg/hour with a 50% Air / 50% Oxygen mixture for the maintenance of general anesthesia.

GROUP P

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Living kidney donors aged between 18 and 65 years.
• Scheduled for an elective donor nephrectomy operation under general anesthesia.
• American Society of Anesthesiologists (ASA) physical status I or II.
• Body Mass Index (BMI) strictly less than 35 kg/m².
• Provided written informed voluntary consent to participate in the study.

You may not qualify if:

• Known history or clinical diagnosis of malignancy or Diabetes Mellitus (DM).
• Active or history of chronic systemic inflammatory or autoimmune diseases.
• Chronic use of analgesics or documented history of substance abuse.
• Known hypersensitivity or allergic reaction to any of the anesthetic agents used in the study (Sevoflurane or Propofol).
• Diagnosed with dementia, severe cognitive impairment, or any significant psychiatric disorder.

Sponsors & Collaborators

• University of Gaziantep: lead

Study Sites (1)

Gaziantep University Sahinbey Research and Application Hospital

Gaziantep, Sahinbey, 27310, Turkey (Türkiye)

RECRUITING

MeSH Terms

Interventions

Sevoflurane; Propofol

Intervention Hierarchy (Ancestors)

Methyl Ethers; Ethers; Organic Chemicals; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Rauf Gul, Professor Doctor

  Gaziantep University Sahinbey Research and Application Hospital

  STUDY CHAIR

Central Study Contacts

Elife SEVİLİR, Medical Doctor

CONTACT

+905423794800; esev1234@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Due to the nature of administering different anesthetic regimes (inhalation vs. total intravenous anesthesia), the attending anesthesia care providers cannot be masked during the surgical procedure. However, the study is masked for participants and outcomes assessors. The laboratory researchers performing the plasma microRNA isolation and RT-PCR expression analyses will be completely blinded to the anesthetic group allocations, identifying samples solely by their designated file numbers.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR DOCTOR

Model Details: This is a prospective, randomized, comparative study utilizing a parallel-group design with a 1:1 allocation ratio. Eligible living kidney donors are assigned to one of two general anesthesia maintenance regimens (Group S: Sevoflurane or Group P: Propofol-TIVA) using a computer-generated random numbers table via block randomization with sequentially numbered, opaque, sealed envelopes to ensure strict allocation concealment.

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: August 12, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: August 12, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)