Effects of Desflurane and Sevoflurane anesthesia on regulatory T cells in patients undergoing living donor kidney transplantation: a randomized intervention trial

Arpa Chutipongtanate, Sasichol Prukviwat, Nutkridta Pongsakul, Supanart Srisala, Nakarin Kamanee, Nuttapon Arpornsujaritkun, Goragoch Gesprasert, Nopporn Apiwattanakul, Suradej Hongeng, Wichai Ittichaikulthol, Vasant Sumethkul, Somchai Chutipongtanate, Arpa Chutipongtanate, Sasichol Prukviwat, Nutkridta Pongsakul, Supanart Srisala, Nakarin Kamanee, Nuttapon Arpornsujaritkun, Goragoch Gesprasert, Nopporn Apiwattanakul, Suradej Hongeng, Wichai Ittichaikulthol, Vasant Sumethkul, Somchai Chutipongtanate

Abstract

Background: Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation.

Methods: A prospective, randomized, double-blind trial in living donor kidney transplant recipients was conducted at a single center, tertiary-care, academic university hospital in Thailand during August 2015 - June 2017. Sixty-six patients were assessed for eligibility and 40 patients who fulfilled the study requirement were equally randomized and allocated to desflurane versus sevoflurane anesthesia during transplant surgery. The primary outcome included absolute changes of peripheral blood CD4+CD25+FoxP3+Tregs which measured by flow cytometry and expressed as the percentage of the total population of CD4+ T lymphocytes at pre-exposure (0-h) and post-exposure (2-h and 24-h) to anesthetic gas. P-value < 0.05 denoted statistical significance.

Results: Demographic data were comparable between groups. No statistical difference of peripheral blood Tregs between desflurane and sevoflurane groups observed at the baseline pre-exposure (3.6 ± 0.4% vs. 3.1 ± 0.4%; p = 0.371) and 2-h post-exposure (3.0 ± 0.3% vs. 3.5 ± 0.4%; p = 0.319). At 24-h post-exposure, peripheral blood Tregs was significantly higher in desflurane group (5.8 ± 0.5% vs. 4.1 ± 0.3%; p = 0.008). Within group analysis showed patients receiving desflurane, but not sevoflurane, had 2.7% increase in peripheral blood Treg over 24-h period (p < 0.001).

Conclusion: This study provides the clinical trial-based evidence that desflurane induced peripheral blood Tregs increment after 24-h exposure, which could be beneficial in the context of kidney transplantation. Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future.

Trial registration: ClinicalTrials.gov, NCT02559297 . Registered 22 September 2015 - retrospectively registered.

Keywords: Clinical trial; Inhalation agent; Kidney transplant; Tregs; Volatile anesthesia.

Conflict of interest statement

The authors declare no conflict of interests.

Figures

Fig. 1
Fig. 1
Flow diagram of study participants
Fig. 2
Fig. 2
Effects of desflurane and sevoflurane anesthesia on the CD4 + CD25 + FoxP3+ Tregs (n = 20 per group). a Representative gating strategy of Treg enumeration. b The percentage of Treg in the CD4 + cell population. c The absolute number of white blood cells (left), and the calculated numbers of CD4 + cells (center) and Treg (right), in peripheral blood (details in the Method section). The result showed that the LDKT patients who received desflurane anesthesia, but not sevoflurane, had significantly increased Tregs in the peripheral blood at 24-h post-exposure. All experiments were performed in triplicate. Des, desflurane; NS, not significant; Sevo, sevoflurane
Fig. 3
Fig. 3
Plasma cytokines were measured by multiplex cytokine immunoassay. Box plots exhibited plasma levels of anti-inflammatory cytokines IL-10 and TGF-β1, and pro-inflammatory cytokines GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-12, IL-13 and TNF-α (n = 26; 14 desflurane, 12 sevoflurane). IL-10 showed an increased trend over 24-h period in patients receiving desflurane anesthesia. Des, desflurane; Sevo, sevoflurane
Fig. 4
Fig. 4
Matched-pair data analysis of Tregs and IL-10 (n = 26; 14 desflurane, 12 sevoflurane). Fold change was calculated by Tregs (or IL-10) measured at 24-h divided by that of pre-exposure (0-h) in the same patient, in which fold change > 1 indicated upregulation and fold change < 1 was downregulation. a Scatter plot exhibited the positive relationship between Tregs and IL-10 fold changes. b Bar plots showed a higher proportion of co-increased Tregs and IL-10 immunophenotypic response in patients receiving desflurane anesthesia. Des, desflurane; Sevo, sevoflurane

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