Effects of Sevoflurane and Desflurane on Treg

Study Overview
=================
Brief Summary
-----------------
This prospective interventional study aims to compare sevoflurane and desflurane anesthetic agents on regulatory T cell (Treg) numbers and its cytokine production in patients undergoing Living Donor Kidney Transplant (LDKT).

Detailed Description
-----------------
All patients with end stage renal disease (ESRD) need renal replacement therapy, either dialysis or kidney transplantation. Dialysis, despite its effectiveness in prolonging ESRD patients' lives, is a burden. Successfulness in kidney transplantation will restore good quality of life in ESRD patients. However, one of the most important complications that lead to transplant failure is graft rejection. It is already known that the pathophysiology of the rejection is immune response. Recent evidence showed that regulatory T cell (Treg) plays a central role in preventing graft rejection by inhibiting recipient alloimmune response (1-3). Characterization of Treg numbers and/or functional changes under various conditions may lead to a new preventive measure and/or a novel therapeutic strategy for graft rejection. Kidney transplantation is conducted under general anesthesia. Interestingly, several agents used in general anesthesia have also modulated immune functions (4-12). Although the effect of inhalation anesthetic agents on leukocyte count has been shown, the effect on Treg function has totally been unknown. Knowing the effects of inhalation agents on Treg numbers and functions will be beneficial to intraoperative management during transplant surgery, aiming toward reducing the risk of graft rejection in the future.

Official Title
-----------------
Effects of Sevoflurane and Desflurane Anesthesia on Regulatory T Cells in Patients Undergoing Living Donor Kidney Transplantation

Conditions
-----------------
Transplant; Failure, Kidney

Intervention / Treatment
-----------------
* Drug: Sevoflurane
* Drug: Desflurane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients receiving 1st living donor kidney transplantation Exclusion Criteria: Hyperacute graft rejection Pre-existing autoimmune or immunodeficiency diseases in recipients Receiving blood product during 24-h perioperative period Patient refuse to participate this study at any time point

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sevoflurane<br>In sevoflurane arm (n=20) at the beginning after successful intubation, 2 L/min nitric oxide (N2O), 2 L/min O2 , and 2% to 2.5% sevoflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 minimal alveolar concentration (MAC) of sevoflurane in 50% O2 and 50% N2O. | Drug: Sevoflurane<br>* After induction of anesthesia and successful intubation, 2 L/min N2O, 2 L/min O2 , and 2% to 2.5% sevoflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 minimal alveolar concentration (MAC) of sevoflurane in 50% O2 and 50% N2O. Ventilation will be adjusted to keep end-tidal carbon dioxide 30-35 mmHg (Tidal volume 7-10 mL/kg).<br>* Other names: Ultane;|
| Experimental: Desflurane<br>In desflurane arm (n=20) at the beginning after successful intubation, 2 L/min N2O, 2 L/min O2, and 6% to 8% desflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 MAC of desflurane in 50% O2 and 50% N2O. | Drug: Desflurane<br>* After induction of anesthesia and successful intubation, 2 L/min N2O, 2 L/min O2 , and 6% to 8% desflurane will be given for 10 minutes then total flow will be decreased to 2 L/min. Anesthesia will be maintained using 1-1.5 minimal alveolar concentration (MAC) of desflurane in 50% O2 and 50% N2O. Ventilation will be adjusted to keep end-tidal carbon dioxide 30-35 mmHg (Tidal volume 7-10 mL/kg).<br>* Other names: Suprane;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of regulatory T cells | Assessing change of Treg numbers by flow cytometry from baseline (before exposure to sevoflurane or desflurane) to after exposure to sevoflurane or desflurane for 2-h and 24-h | Within 24-h peri-operative period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T lymphocyte cytokine production | Assessing change of T lymphocyte cytokine production using Multiplex immunoassay of interleukin (IL)-10, Tumor Necrosis Factor (TGF)-beta, IL-2, Interferon (IFN)-gamma, IL-4, IL-5, IL-13, from baseline (before exposure to sevoflurane or desflurane) to after exposure to sevoflurane or desflurane for 2-h and 24-h | Within 24-h peri-operative period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Regulatory T cells, Sevoflurane, Desflurane, Cytokines, Flow cytometry, Living Donor Kidney Transplant