Comparative Effects of Propofol and Sevoflurane Anesthesia in Living Kidney Donors on Perioperative Plasma miR-146a, miR-155, and miR-21 Levels: A Randomized Prospective Comparative Trial

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.