Graft Failure, Ischemia-reperfusion Injury
Conditions
Keywords
Renal Transplantation, Ischemia-reperfusion injury, Heme-oxygenase 1, Heme arginate
Brief summary
This is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants. The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.
Detailed description
Patients will be recruited from the East of Scotland transplant waiting list and consent when they arrive in the hospital. The investigators will randomise them to drug or placebo and give the infusion prior to induction for their transplant. A blood sample will be taken prior to infusion and a renal biopsy will be taken before the graft is implanted. These will be used as baseline values. Patients will receive standard care from our unit. The investigators will use the routine blood test results (urea and creatinine) to determine the function of the graft. The investigators will take blood samples 24 hours after infusion of drug/placebo and use this to determine the primary outcome. Blood tests will be taken daily and a renal biopsy taken on day 5 to fulfil secondary objectives.
Interventions
DRUGHeme arginate (Normosang)
3mg/kg as a single IV infusion prior to transplant over 30 mins and same dose repeated on day 2 post-transplantation. Each drug infusion will be followed by 100ml saline IV to flush the line.
DRUG0.9% sodium chloride
Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug.
Sponsors
NHS Lothian
University of Edinburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* all patients receiving a cadaveric single kidney transplant * patients on a standard immunosuppressive regime
Exclusion criteria
* patients on different immunosuppressives * patients receiving 3rd or subsequent kidney transplant * patients are fully anti-coagulated * patients unable to take Heme Arginate * patients unable to give informed consent * patients on combined anti-platelet agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Macrophage/monocyte HO-1 protein levels | 24 hours | We will measure the level of HO-1 protein in isolated macrophages/ monocytes in a peripheral blood sample taken at 24 hours after drug infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect on transplanted kidney function | daily for 5 days | We will record how the kidney functions by determining presence or absence of delayed graft function. |
| Macrophage/monocyte HO-1 mRNA levels | 24 hours | We will measure HO-1 mRNA levels in macrophages/monocytes from a peripheral blood sample taken at 24 hours. |
| Urinary biomarkers as markers of injury | daily for 5 days | We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function. |
| HO-1 protein in kidney transplant | 5 days | We will measure the level of HO-1 protein in kidney tissue from a biopsy sample taken 5 days after drug infusion. This will be compared to baseline |
Countries
United Kingdom
Outcome results
None listed