The aim of this study is to evaluate logistic challenges of normothermic machine perfusion in transplant candidate allocated in the ESP
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure will be the logistic challenges in including
patients and treatment with normothermic ex vivo kidney perfusion (e.g. failed
perfusion procedures, renal artery or vein thrombosis, participation rate).
Secondary outcome
1. Renal histology at start and end of normothermic perfusion
2. Measured glomerular filtration rate * the best surrogate of graft function *
(first 4 weeks, 3-months post-transplant), which is considered to be a
predictor of long term kidney graft survival as well.
3. 3-month graft (censored and uncensored for recipient death) and patient
survival
4. Incidence and severity of delayed graft function defined as the need for
dialysis within the first 7 days after kidney transplantation and preceding the
return of kidney function. *
5. Incidence of primary non-function (PNF) defined as the permanent lack of
function of the graft from time of transplantation until months
post-transplant. This endpoint is determined post-hoc at 3 months
post-transplant. *
6. Biopsy proven acute rejection within 3 months post-transplant.
Background summary
Ageing of the European population has impact on various domains in health care,
including renal insufficiency and kidney transplantation. In 1999 the
Eurotransplant Senior Program (ESP) was launched to allocate kidneys from older
(*65 years) deceased donors to older (*65 years) local or regional transplant
candidates, to keep both ischemia and waiting times low and thereby improve the
rate and outcome in elderly transplant recipients. Recently, the short and
long-term graft and patient survival of the ESP was reported to be worse as
compared to the outcome of the regular renal transplant program. Moreover, the
5-year mortality rate of elderly recipients of elderly kidneys is comparable to
that of waitlisted elderly patients on dialysis, thereby demonstrating the
limited success of the ESP.
Optimizing these older donor kidneys on machine perfusion may be a successful
approach to improve the outcome. Compared to cold storage, hypothermic machine
perfusion has shown a reduced risk of delayed graft function and improved graft
survival in the first year after transplantation. Normothermic kidney perfusion
is a relative novel technique that may recondition the kidney and restore renal
function prior to transplantation. Clinical studies on marginal donors show
that the technique is safe and suggest that early graft function may be
improved. More-over, normothermic machine perfusion might lead to a better
evaluation of the quality of the to-be-implanted organ.
Given the poor results of the ESP, we expect that especially this group of
kidney recipient might benefit the most from an effort to improve organ quality
by normothermic machine perfusion. To date, evidence from a randomized
controlled to support the concept is not available and needed to legitimize the
costly approach using machine perfusion and ex vivo manipulation.
Study objective
The aim of this study is to evaluate logistic challenges of normothermic
machine perfusion in transplant candidate allocated in the ESP
Study design
Pilot study prior to a randomized controlled trial with including a total of 10
patients.
Intervention
At the Erasmus MC operating room complex, the donor kidney(s) will be unpacked
under sterile conditions, benched to assess acceptability for transplantation.
During the benching, 2 pre-defined biopsies from both poles of the kidney will
be taken as baseline values to determine markers of kidney damage and aging.
Hereafter, the kidney will be placed on to the normothermic organ perfusion
machine. The kidney will be rinsed with 500 ml preservation solution and then
pumped for two hours at 37 degrees Celsius with an oxygenated plasma-free red
cell*based solution at a pressure of 75 mmHg. Nutrients, glucose, and
prostacyclin will be infused at a set rate to maintain homeostasis. During
normothermic ex vivo kidney perfusion, the quality of each kidney will be
assessed. The assessment will be based on the macroscopic appearance, the mean
renal blood flow, the total amount of urine produced. After two hours of
normothermic ex vivo kidney perfusion, the machine will be switched to
hypothermic perfusion modus, gradually cooling down the donor kidney. After
cooling down the kidney will be rinsed with 500 ml preservation solution and
packed on cold storage.
Study burden and risks
Kidney transplantation will be performed by well-trained transplant surgeons.
Hypothetically, the normothermic machine perfusion might fail, however during
extensive testing no failures were observed. If a failure has been identified,
we can quickly switch to cold storage. Therefore an acceptable risk of the
normothermic machine perfusion is to be expected.
Renal biopsies are obtained during machine perfusion (start and finish). These
biopsies have been shown to possess no risk to the patient. No extra vena
puncture for blood sampling will be performed as all will be combined with
routine vena puncture. The total amount of blood samples taken is 100 ml during
the study.
The most important benefit from participation is the prospect of a better
functioning graft post-transplant.
's-Gravendijkwal 230
Rotterdam 3015CE
NL
's-Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
- Recipient age * 65 yr
- Listed for renal transplantation due to end stage renal disease on the ET list
Exclusion criteria
- Donor kidney which is unsuitable for transplantation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL63063.078.17 |