Propofol and sevoflurane anesthesia acutely mediate different transcriptional effects in the porcine kidney

Background: Volatile anesthetics (sevoflurane, isoflurane) have been demonstrated to impair renal function as in increased renal vasoconstriction, reduced renal blood flow, and reduced oxygen delivery. Volatiles have also been associated with higher incidence of acute kidney injury. If volatiles also mediate acute subcellular changes in the kidney remains undefined. Therefore, we aimed to investigate renal transcriptomics in an experimental pig model with either intravenous (propofol) or volatile (sevoflurane) anesthesia. Methods: Renal tissue from pigs anesthetized with different anesthetics (snap frozen renal cortex and medulla) were used for RNA sequencing. Anesthesia was maintained for approximately four hours at similar anesthetic depth before tissue was harvested. Propofol was given at 10 mg/kg/h and sevoflurane was kept at 0.9 minimal alveolar concentration. A total of 23 samples were analyzed: 9 cortex (6 propofol, 3 sevoflurane) and 14 medulla (7 propofol, 7 sevoflurane). Reads were mapped to pig genome Sus scrofa (Sscrofa11.1) using the STAR program. Differentially expressed genes (DEGs) were identified across anesthesia type and kidney region using DESeq2. Over-Representation Analysis was used for pathway enrichment analysis via the ClusterProfiler package. Results: Comparing propofol vs sevoflurane revealed 104 DEGs. Regional analysis showed only 1 unannotated gene change in the cortex. In the medulla, 42 DEGs were significantly different between propofol and sevoflurane. Propofol mediated upregulation in medullary metabolism-associated genes (Cyp24a1, Gatm). Sevoflurane upregulated medullary expression of the glutamate transporter Slc1a2. Also, genes associated with oxidative stress and hypoxia were upregulated in renal medulla from sevoflurane anesthetized pigs (apolipoprotein D ApoD, Hif3a). Furthermore, genes with greater expression in propofol were enriched in cell cycle (GO GO:0022402) and chromosome segregation (GO:0007059) pathways. Conclusion: Propofol and sevoflurane anesthesia acutely mediate different transcriptomic outcomes in the kidney. This is more pronounced in the medulla where propofol up-regulates metabolism-associated and mitosis related genes and sevoflurane up-regulates synaptic transporters and hypoxia and oxidative stress associated genes. If these transcriptomic effects of different anesthetics are mediated by inter-organ crosstalk, direct molecular alterations, or hemodynamic changes remains unclear. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.