The use of the Airdrive* machine perfusion system in graft preservation during kidney transplantation: a pilot study in kidney transplantation of grafts from post-mortem donors.

Kidney donor graft shortage for transplantation has led to the use of marginal
donors such as non-heart beating donor (NHBD) kidneys. As perfusion in this
category of donor patients is absent prior to graft nephrectomy, NHBD kidneys
suffer warm ischemia, causing damage, which is associated with early and late
graft loss. Preservation of the graft by hypothermic machine perfusion instead
of conventional cold static storage provides a viable solution to reduce the
warm ischemic damage-induced graft loss. In preclinical animal studies, the
Airdrive* machine perfusion system has shown to be safe, and to improve renal
function and graft structural integrity after induced warm ischemic damage. The
next step is to introduce the Airdrive* system in a clinical setting. To this
end, a pilot-study using the Airdrive* system for the preservation of kidney
grafts was devised to demonstrate that the machine perfusion system is *safe*
for use in the clinical setting. In this pilot-study we hypothesize that the
use of the Airdrive* machine perfusion system is safe and technically feasible
for graft preservation in kidney transplantation.

The objective is to assess the safety profile of the hypothermic Airdrive*
oxygenated machine perfusion system for graft preservation in kidney
transplantation.

In this prospective pilot study recipients of kidney grafts from post-mortem
donors are recruited by the transplant surgeon. The recipients will be included
after having given informed consent. Before surgery, after arrival and
inspection of the cold stored kidney graft in the AMC, the graft will be washed
out using Belzer*s University of Wisconsin machine perfusion solution (UW-MPS)
. When the graft is completely flushed, hypothermic machine perfusion
preservation starts by connecting the renal artery of the graft to the
Airdrive* machine perfusion system instead of a continuation of cold static
storage. Airdrive* machine preservation ends approximately 3 hours later, just
before implantation of the graft in the recipient. In case of failure of the
pump system, preservation of the graft falls back to static cold storage as the
cold environment is maintained until transplantation. Except for the use of
machine perfusion, the entire transplantation procedure as well as the
investigational follow-up will comply with standard clinical practice for
kidney transplantation of grafts from post-mortem donors (including blood and
urine sampling). During the machine perfusion and transplantation procedure,
possible side effects which may be attributable the use of the Airdrive* are
monitored and recorded. During the transplant procedure and shortly thereafter,
vital parameters (among others, pulse and blood pressure) will be monitored to
assess possible adverse effects of the use of Airdrive* machine preservation.
Also, after the transplantation procedure has been completed, the recipient
will be observed to monitor possible adverse reactions. Postoperative recovery
during admission will be evaluated (physical condition, blood sampling, urine
sampling). After discharge, follow-up will continue until 1 month after
transplantation.

The kidney graft recipients require kidney transplantation, according to
standard clinical indications. Washout of the graft and hypothermic storage
until implantation into the recipient is also part of normal preparations for
transplantation of solid organs. In this study the clinical standard organ
preservation method (cold static storage) applied in the time between arrival
of the kidney graft and implantation in the recipient, will be replaced by
hypothermic Airdrive* machine perfusion preservation of the graft.
Additionally, the clinical standard organ preservation solution (i.e., UW-CS)
will be replaced with the same type of preservation solution modified for
optimal machine perfusion (i.e., UW-MPS).
Although not the purpose of this study, there might be a direct advantage for
the kidney recipient, as the function of the graft retrieved from post-mortem
nephrectomy may be impaired due to warm ischemic-exposure and/or prolonged cold
ischemic times. In these cases, the use of machine perfusion preservation of
the graft has shown to be a benefit. Risks other than the usual risks
associated with undergoing kidney transplantation of grafts from post-mortem
donors, are possible risks related to adverse effects of the use of the
Airdrive* system for preservation of the graft prior to transplantation. As
side effects that could be attributed to the use of the Airdrive* system have
not been encountered in the preclinical trials, possible adverse effects are
not anticipated, however need to be confirmed in the clinical setting.