Dexmedetomidine and Kidney Transplantation

Study design

• Study type

o Multi-center, Double blinded, placebo controlled, randomized trial

• Primary and secondary outcomes

• Primary outcomes Difference in mean kinetic GFR at post operative day (POD) 1 between intervention and control group.
• Secondary outcomes Incidence of DGF Per- and post-operative urine output Post-operative creatinine levels Time with hypotension <30% of pre-induction value Mean and median intraoperative norepinephrine Incidence of bradycardia requiring emergency treatment intraoperatively Amount of fluid administered intraoperatively Levels of renal function bio-markers (see table 1) on POD 1-2-3 Incidence of pathological radiological findings on post-operative renal ultrasound at POD 1 Evaluation of the evolution of cytological parameters of the grafts in the two groups Incidence of graft rejection during the first year after the transplantation Length of hospital and IMC/ICU stay Incidence of respiratory complications
• Population

o After approval from the Ethics Commission of the Canton of Geneva, and after obtaining the consent of the patients, the investigators will include in the study all patients admitted for renal transplantation according to the following criteria in the study: Inclusion criteria

a. Elective and urgent renal transplantation for end-stage renal insufficiency. Exclusion criteria

• Age < 18 years old
• Any known allergy or hypersensitivity to dexmedetomidine or clonidine
• Preoperative bradycardia with heart rate <50
• Second or third-degree atrioventricular block
• Left ventricular ejection fraction <30%
• Preoperative severe systolic dysfunction (LVEF<30%)
• Conduction disorders of the Mobitz 2 or Mobitz 3 type in the absence of a pacemaker
• Exposure to Dexmedetomidine in the past 30 days
• Recent cerebrovascular pathology (< 3 month)
• Data collection and measurements o Baseline data: Age, sex Months on waiting list Diabetes status Hypertension status Donor baseline creatinine and eGFR Recipient baseline creatinine and eGFR (if available)

DESCRIPTION OF STUDY PROCEDURES

Per- and Post-operative Urine Output This is a routine standard of care and will be assessed during and after the surgery daily and will allow to monitor kidney function assessing the response to the study drug Urine sample This is a routine standard of care. This will be performed before, during and after surgery to assess kidney function and reactions to given diuretics. This will allow the investigators to monitor different factors permitting better understanding of responses to the study drug.

Blood sample This is a routine standard of care and will be taken during and after the surgery (day 1 to 7 during the participants stay, then 1 and 6 months after and finally 1 year after the surgery) and will allow the investigators to monitor body's reaction to given drugs, kidney and heart function and monitor for any adverse reactions from administered drugs.

The investigators will use it to monitor different factors (including renal function bio-markers) to assess the status of the new kidney and reactions to the study drug.

Graft ultrasound This is a noninvasive procedure and the routine standard of care. Ultrasound of kidney graft will be done every post-operative day until proof of adequate graft function.

Graft biopsy This is a routine procedure and the standard of care after kidney transplantation. This will be done once during the operation, after graft reperfusion and at 6 months post transplantation.

Inclusion criteria

• Elective and urgent renal transplantation for end-stage renal insufficiency

Exclusion criteria

• Age < 18 years old
• Any known allergy or hypersensitivity to dexmedetomidine or clonidine
• Preoperative bradycardia with heart rate <50
• Second or third-degree atrioventricular block
• Left ventricular ejection fraction <30%
• Preoperative severe systolic dysfunction (LVEF<30%)
• Conduction disorders of the Mobitz 2 or Mobitz 3 type in the absence of a pacemaker
• Exposure to Dexmedetomidine in the past 30 days
• Recent cerebrovascular pathology (< 3 month)