Volatile Anesthetic Protection Of Renal transplants 2

Volatile anesthetics (VA) like sevoflurane and isoflurane have the ability to
reduce ischemia and reperfusion injury (IRI) (1). This phenomenon is called
anesthetic conditioning (AC). Depending on the timing of administration of the
anesthetic it is defined as pre- (before ischemia), per- (during ischemia) or
post- (directly upon reperfusion) conditioning. Protective effects of AC on the
heart have been demonstrated in vitro, in various animal species and in
randomized controlled clinical trials (2-7). In contrast evidence for AC in the
kidney is restricted to in vitro and animal work (8-11).
Since IRI is inevitable in organ transplantation and AC could be an effective
way to reduce IRI, we designed the VAPOR trial. The Volatile Anesthetic
Protection Of Renal transplants trial is a two-step study looking at the effect
of two commonly used anesthetic agents on the renal outcome in kidney
transplantation. As a first step we conducted the VAPOR-1 (Volatile Anesthetic
Protection of Renal Transplants-1) trial. A randomized controlled clinical
trial evaluating the influence of two common anaesthetic regimens, a propofol
based anesthesia vs. a sevoflurane based anesthesia, on transplant outcome in
living donor kidney transplantation (LDKT). We chose LDKT as a first step since
it is a homogenous and reproducible model of kidney transplantation with high
quality donors and similar ischemia times. However, the rate of failure for
LDKT defined as delayed graft function (DGF) is low (<5%). We therefore
considered VAPOR-1 a proof-of-concept in which we focused on a urinary
biomarker level reflecting kidney injury.
Sixty couples were assigned to three groups: PROP; donor and recipient received
propofol, SEVO; donor and recipient received sevoflurane and PROSE; donor
received propofol and recipient received sevoflurane (n=20/group). A
sevoflurane-based anesthesia lead to higher urinary levels of KIM-1 and NAG but
not H-FABP compared to a propofol-based anesthesia. This was not reflected in a
worse graft outcome. After a follow up period of 2 years there was a
significant difference in acute rejection in favour of the sevoflurane groups.
In conclusion, sevoflurane based anesthesia was associated with higher urinary
KIM-1 and NAG levels in LDKT however this was not reflected in inferior graft
outcome. Remarkably a lower acute rejection rate was seen in the sevoflurane
groups. It is known that parenchymal injury during the transplantation process
due to IRI can make the graft more prone to acute and chronic rejection. When
reproducible, these findings may have important implication for
transplantation. The use of volatile anesthetics is not associated with extra
costs and can be implemented very easily since volatile anesthetic regimens are
widely used and generally accepted. We therefore would like to proceed with the
VAPOR-2 trial, a multicenter trial comparing these 2 anesthetic agents in renal
transplantation with kidneys of DBD and DCD donors powered on delayed graft
function, an adequate reflection of ischemia and reperfusion injury. within the
first week after transplantation

To compare the effect of a sevoflurane based anesthesia versus a propofol based
anesthesia on acute rejection and outcome in recipients of living, DCD and DBD
donor kidneys.

Prospective randomized controlled European multicenter clinical trial with two
parallel groups

Patients will be included and randomised to one of the following groups:
Group 1 PROP (control): propofol: a propofol-remifentanil based general
anesthesia.
Group 2 SEVO (intervention): Sevoflurane: a sevoflurane-remifentanil based
general anesthesia.

There are no significant additional risks or burdens for participating
patients. Both anesthetic techniques are standard of care and clinically
applied during kidney transplantation.
The total volume of blood sampling has no clinical impact. With exception of
the second bloodsample (T1) all samples will be combined with blood samples
taken routinely after each kidney transplantation in participating hospital.
Sample T1 will be taken during the transplantation when the patient is under
general anesthesia.
The extra study blood samples will thus have no additional burden for the
patient. Urine sampling has no burden or risk for both donor and recipient and
is part of the routine postoperative care for the renal transplant patient.