Kidney injury after transplantation Urological and Genital Diseases Surgical operation with transplant of whole organ
Conditions
Interventions
Patients will be randomised to either receive RPC during transplantation or the standard transplant with sham procedure
Sponsors
University of Leicester (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age greater than or equal to 18 years 2. Patients receiving a primary or secondary renal allograft from a live or donation after Brain Stem Death (DBD donor) 3. Patients with second transplants must have maintained their primary graft for at least six months after transplantation (with the exception of graft failure due to technical reasons) 4. Signed written informed consent
Exclusion criteria
Exclusion criteria: 1. Blood type ABO incompatible live donor transplants 2. Donation after cardiac death donors 3. Patients with severe peripheral vascular disease 4. Patients on ATP-sensitive potassium channel opening or blocking drugs
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Live donor: 1. Slow graft function measured by creatinine fall in the first 24 hours and Area under the curve (AUC) serum creatinine over the first 7 days post transplant 2. Graft function rates: incidences of delayed graft function and primary non-function 3. Glomerular filtration rate (eGFR) and serum creatinine levels: 1 and 3 months 4. Graft survival 5. Patient survival 6. Episodes of rejection within the first 3 months (cell and antibody mediated) Deceased donor: 1. Slow graft function measured by creatinine fall in the first 24 hours and Area under the curve (AUC) serum creatinine over the first 7 days post transplant 2. Graft function; incidences of delayed graft function and primary non-function 3. Glomerular filtration rate (eGFR) and serum creatinine levels: 1 and 3 months 4. Graft survival 5. Patient survival 6. Episodes of rejection within the first 3 months (cell and antibody mediated) | — |
Secondary
| Measure | Time frame |
|---|---|
| Live and deceased donor: In addition, we wish to further understand the mechanisms by which remote postconditioning (RPC) conveys its protective actions. 1. The renal blood flow into the kidney in the immediate post transplant phase will be measured using a Doppler flow probe. The renal vascular resistance will be calculated from the kidney weight and renal arterial blood flow 2. Mediators of RPC: Nitric oxide levels and adenosine levels determined by ELISA using plasma samples taken from the renal vein 30 minutes after reperfusion and from peripheral venous samples (see blood sample protocol) 3. Markers of ischaemic injury: Neutrophil gelatinase-associated lipocalin (NGAL)- small protein that is increased with ischaemic injury, KIM-1, Oxidative damage (protein carbonyl, Lipid peroxidation, DNA damage), Inflammation; levels of cytokines (IL-1, IL-©¬, IL-2, IL-6, IL-8, IL-10, TNF-¥á), determined using plasma and urine samples 4. Measure the level of repair: Determination of up and down regulated genes using gene array analysis in renal biopsies. The presence of genes such as those involved in apoptosis (anti-apoptotic Bcl-2), Protection [Hemeoxygenase-1 (HO-1) and Heat shock protein (HSP)] and fibrosis will be validated by RT-PCR. 5. Histological changes: Biopsies will be stained with H&E for histological scoring, immunohistochemistry techniques to determine injury and Sirius red (an extracellular matrix stain) to measure interstitial fibrosis | — |
Countries
United Kingdom
Outcome results
None listed