First, to determine the extent to which oxidative stress and microcirculatory perfusion defects occur during clinical kidney transplantation. Second, to study the relationship between these events and kidney function, inflammation and renal cellular…
ID
Source
Brief title
Condition
- Nephropathies
- Vascular therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Oxidative stress:
1. Renal arterio-venous difference in plasma F2-isoprostanes concentration.
2. Tissue F2-isoprostanes concentration.
3. Urine F2-isoprostanes concentration.
4. Advanced glycation end products (AGE*s) measured by skin autofluorescence.
Renal perfusion:
1. Renal artery flow measured by Laser-Doppler flow probe.
2. Microcirculatory perfusion measured by OPS imaging (parameters: volumetric
blood flow, functional capillary density).
Secondary outcome
Kidney function:
1. Dialysis dependency after transplantation.
2. Area under the curve for serum creatinine concentration over time (14 days).
3. Fractional excretion of sodium (14 days).
Inflammation: Serum cytokine concentrations (IFN-γ, TNF-α, IL-6, IL-10, IL-17,
IL-23).
Renal cellular injury: Urine NGAL and NAG concentrations.
Anti-oxidants: vitamin C, vitamin E, GSH/GSSG ratio, total anti-oxidant
capacity.
Endothelial glycocalyx:
1. Thickness measured by OPS imaging
2. Renal arterio-venous differences in syndecan-1, heparin sulphate and
hyaluronan concentrations.
Background summary
In animal models, oxidative stress and microcirculatory perfusion defects have
been shown to cause renal ischemia/reperfusion injury. The discovery of
F2-isoprostanes as markers of lipid peroxidation and orthogonal polarization
spectral (OPS) imaging of the human microcirculation allow accurately study of
these phenomena in clinical settings. This may lead to rational selection of
interventional strategies for ischemic acute renal failure and may provide
surrogate outcome measures for clinical trials.
Study objective
First, to determine the extent to which oxidative stress and microcirculatory
perfusion defects occur during clinical kidney transplantation. Second, to
study the relationship between these events and kidney function, inflammation
and renal cellular injury. Third, to study the depletion of anti-oxidants to
guide selection of interventions for future clinical trials. Fourth, to study
the breakdown of the endothelial glycocalyx during renal ischemia/reperfusion
injury.
Study design
Observational study.
Study burden and risks
During surgery, 6 blood samples of 10.5 mL will be taken from an arterial line
and 4 blood samples of 10.5 mL from the renal vein (already exposed).
Furthermore, 4 needle biopsies will be taken from the kidney. Taking these
samples may be associated with bleeding from the puncture site that can be
controlled during surgery. OPS imaging of the renal microcirculation and
measurement of renal artery flow do not expose the patient to additional risks.
Surgery will take approximately 15 minutes longer to allow these measurements
to take place. During and after surgery, AGE*s are measured non-invasively with
skin autofluorescence. This takes approximately 5 minutes and does not expose
the patient to any risks. After surgery, 4 venous blood samples of 5 mL will be
taken from a peripheral venous catheter (already present). Urine will be
collected from the urinary catheter during the first 4 post-operative days
(already present). All measurements will be done while the patient is admitted
to the hospital. Physical and psychological discomfort from participating in
study should be minimal. The patient will not benefit directly from the study;
however, this study paves the way for interventional studies from which benefit
for the patient is expected.
P. Debyelaan 25
6229 HX Maastricht
Nederland
P. Debyelaan 25
6229 HX Maastricht
Nederland
Listed location countries
Age
Inclusion criteria
Kidney transplant recipient (living donor [and their donors] / deceased heart-beating donor / deceased non-heart-beating donor).
Partial nephrectomy with clamping of the renal vascular pedicle.
Exclusion criteria
Age < 18 years
Smoking
Donor > 60 years
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 | NL15732.068.07 |