Primary Objective: -To compare metabolic activity and efficiency directly after transplantation in living and deceased donor kidney grafts. Secondary Objective(s): -To assess whether the contribution of aerobic and anaerobic metabolism differs…
ID
Source
Brief title
Condition
- Renal disorders (excl nephropathies)
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Metabolic activity of the kidney as measured by pO2, pCO2, lactate, glucose and
full lipid profile. The respiratory quotients (RQ) for every time-point will be
calculated.
Secondary outcome
Kidney biopsies taken before (routine clinical biopsy) and after reperfusion
(this study) will be collected in all patients. Biopsy specimens will be snap
frozen and processed to make it suitable for NMR. By NMR different
intermediates of the citric acid cycle will be quantified, to be able to
estimate activity of aerobic metabolism and more accurately to define where
potential problems are.
Since measurements are dependent on flow kinetics and perfusion of the kidney,
flow in the renal artery and microvascular perfusion will be measured as well.
Both will be compared between living and cadaveric donor kidneys. Measurements
of metabolism will be related to microvascular perfusion
We will also measure renal blood flow in the living donor and compare this to
the renal blood flow through the same kidney after transplantation.
Background summary
Kidney transplantation is the treatment of choice for patients with end-stage
renal disease and is accepted as the most advanced form of renal replacement
therapy. As a consequence of organ shortage and long waiting lists, more
marginal donors are accepted. Graft survival for living unrelated donation is
superior compared to grafts from brain dead donors, even though the average
human leukocyte antigen (HLA) matching is worse in living unrelated donation.1
Therefore, the poor graft survival from deceased donors cannot be exclusively
attributed to differences in immunogenicity.
Already during the process of transplantation the graft is exposed to various
events, which may in turn lead to functional deterioration.
Ischemia/reperfusion (I/R) injury is the exacerbation of tissue damage upon
reestablishment of circulation after a period of ischemia. I/R injury is an
inevitable consequence of organ transplantation, and a major determinant of
patient and graft survival. The pathophysiology of I/R injury is complex and
incompletely understood. This complexity in the identified mechanisms leading
to I/R injury may have been one of the reasons why clinical trials inhibiting
specific factors such as complement or cytokines have failed thus far.2,3
This stimulated us to step back and try to assess basic differences between
living and deceased donor kidney transplantation. Preliminary results indicated
an involvement of metabolic activity.
Not much is known on metabolic re-activation after transplantation. Oxygen is
needed for a normal aerobic metabolism, and hypoxia will switch metabolism from
aerobic to anaerobic pathways. Although organs that are preserved for
transplantation are preferentially cooled to 4 ºC, metabolic activity is never
completely diminished. Anaerobic metabolism will result in insufficient ATP
production, deprivation of glycogen reserve and production of toxic metabolic
products, such as lactate. Loss of ATP primarily causes disturbance of cellular
functions such as maintenance of homeostasis and capability of apoptosis. Later
consequences of ATP shortage are insufficient Na/K pump activity and
intracellular accumulation of metabolic products which lead to hyperosmolarity.
Both can cause cell edema in ischemic tissue, which will eventually lead to
loss of cell function or even cell death.
Study objective
Primary Objective:
-To compare metabolic activity and efficiency directly after transplantation in
living and deceased donor kidney grafts.
Secondary Objective(s):
-To assess whether the contribution of aerobic and anaerobic metabolism differs
between living and deceased donor kidney grafts after reperfusion.
-To assess differences between living and deceased donor kidneys in renal
perfusion after transplantation.
-To follow up the renal blood flow from the kidney in the donor and after
transplantation in the recipient and to analyze whether this correlates with
graft function and survival.
-To form a control group by 1 arteriovenous measurement over the donor kidney,
before donation in the living donor.
Study design
In 10 consecutive patients undergoing living donor kidney transplantation and
10 patients undergoing deceased donor kidney transplantation, per-operative
arteriovenous blood samples will be collected. By cannulating the renal artery
and vein, paired arterial en venous blood samples will be collected and
immediately measured on pO2, pCO2, lactate, glucose and full lipid profile. The
respiratory quotients (RQ) for every time-point will be analyzed and uptake of
glucose and release of lactate will be compared between the groups. Since
measurements are dependent on flow kinetics and perfusion of the kidney, flow
in the renal artery and microvascular perfusion will be measured during
reperfusion as well. (Before living donor procedures, renal blood flow will be
measured in the donor, for that there will be a follow up by the flow
measurement in the recipient). Paired kidney biopsies will be collected before
and after reperfusion to assess metabolites of the citric acid cycle in renal
tissue.
Thereby we want to ad a control group of 4 living donors, by performing 1
arteriovenous measurement over the donor kidney, before donation, so we can
validate the measurements over transplantated kidneys.
Study burden and risks
Risks associated with participation can be considered negligible since limited
amounts of blood will be sampled and a very small biopsy will be taken after
reperfusion. We are experienced with the biopsy method and have performed it
safely for many times now, without ever experiencing complications. Since all
samples are collected during the transplantation, the burden for the patient
can be considered minimal.
The renal blood flow measurement in the donor is non-invasive, it does not
increase hospitalization and it is a short measurement. Therefore, we assume
that it is not a great burden.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Recipients of a kidney graft by kidney tranplantation. (20 recipients)
Living donors (10 donors for a pre-surgical measurement of bloodflow in the a.renalis, non-invasive by echo-doppler).4 of these living donors for 1 arterio and 1 venous sample as control measurement during surgery.
Exclusion criteria
Increased risk of bleeding.
Design
Recruitment
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 | NL40612.058.12 |