Quality assessment of kidneys by ex-vivo warm perfusion prior to transplantation

ISRCTN	ISRCTN91315246
DOI	https://doi.org/10.1186/ISRCTN91315246
Protocol serial number	19053
Sponsor	Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Funder	Kidney Research UK

Submission date: 18/05/2016
Registration date: 29/06/2016
Last edited: 26/08/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
In a healthy person, the kidneys are responsible for filtering out the waste products and excess water in the blood, and converting them into urine. If the kidneys suddenly stop working (acute kidney injury) or are suffering from severe, long-term disease of the kidneys (chronic kidney failure) then the body is unable to get rid of the waste products building up in the blood. Eventually, the kidneys are no longer able to support the body’s needs (end stage renal disease) and so a treatment to replace the work of the failed kidneys is needed. Kidney transplantation is the best treatment for end-stage renal disease. Some kidneys that are donated for transplantation are deemed unsuitable for a range of reasons. The decision not to transplant a kidney relies on the judgment of an experienced surgeon but the suitability of a kidney is subject to varying opinion. Without a robust system of testing these kidneys many that may actually be suitable for transplantation are unnecessarily discarded. When kidneys are removed from an organ donor they are normally stored on ice until they are ready to be transplanted. A kidney can be preserved safely at a low temperature in these conditions. However, there is some degree of deterioration and the longer they are left in this condition the more they deteriorate (rather like food that is kept in the fridge). Furthermore, these conditions do not give us any opportunity to assess the quality of the kidney. The warm perfusion technique has been developed that offers the opportunity to test the kidney before it is transplanted. This involves placing the kidney on a machine and passing a warmed, oxygen-rich solution containing red blood cells through it for about one hour. Under these conditions the kidney can start to function again and produce urine. This allows the assessment of the quality of the kidney so it can be decided whether it can be transplanted. This testing can easily be carried out once the kidney arrives at the centre whilst the patient is being prepared for their transplant. The aim of this study is to assess the quality of kidneys that have been declined for transplantation by other transplant centres through the national allocation system and through the fast-tracking system.

Who can participate?
Adult kidney recipients and donor kidneys from deceased donors over the age of 18 which have been rejected for transplantation by several transplant centres and by all the fast-track transplant centres.

What does the study involve?
Kidneys declined for transplantation will be offered into this research study by NHSBT. If they meet the inclusion criteria they will be transplanted into a suitable recipient. Participants are prepared for surgery in the normal way. During this time the kidney is assessed using the warm perfusion technique. If the kidney is suitable for transplantation, participants are not asked to do anything or experience anything that is not standard procedure or care after receiving a transplant. There is a chance that the kidney is deemed unsuitable for transplantation and if this is the case, the transplant procedure would not go ahead. This decision may be made at the last minute after participants have been prepared for surgery. Following their transplant, participants are followed up in the usual way, which involves clinical visits at least twice a week for six weeks and then weekly for a further six weeks. Three months after the transplant a sample of the transplanted kidney is taken using a needle to look for scarring, either in Cambridge or their local centre.

What are the possible benefits and risks of participating?
Participants benefit from receiving a kidney transplant. There are no notable risks involved with participating in this study.

Where is the study run from?
1. Addenbrooke’s Hospital, Cambridge (UK)
2. Guy’s Hospital, London (UK)
3. Freemans Hospital, Newcastle upon Tyne (UK)

When is the study starting and how long is it expected to run for?
April 2015 to November 2020

Who is funding the study?
Kidney Research UK (UK)

Who is the main contact?
Ms Sarah Hosgood
sh744@cam.ac.uk

Contact information

Ms Sarah Hosgood
Public

University of Cambridge
Department of Surgery
Addenbrooke’s Hospital
Level 9
Hill’s Road
Cambridge
CB2 OQQ
United Kingdom

Phone	+44 1223 762002
Email	sh744@cam.ac.uk

Study information

Primary study design	Interventional
Study design	Non-randomised; Interventional; Design type: Treatment, Process of Care, Management of Care
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Quality assessment of human kidneys by ex-vivo normothermic perfusion prior to transplantation
Study objectives	The aim of this study is to assess the quality of kidneys that have been declined for transplantation by other transplant centres through the national allocation system and through the fast-tracking system.
Ethics approval(s)	East of England - Cambridge South Research Ethics Committee, 30/06/2015, ref: 15/EE/0175
Health condition(s) or problem(s) studied	Kidney transplantation
Intervention	Kidneys declined for transplantation will be offered into this research study by NHSBT. If they meet the inclusion criteria they will be transplanted into a suitable recipient. The patient will be prepared for surgery in the normal way. During this time the kidney will be assessed using the normothermic perfusion technology. The kidney will be perfused with a packed red blood based solution at near body temperature for 60 minutes. If suitable for transplantation, the patient will not be asked to do anything or experience anything that is not standard procedure or care after receiving a transplant. There is a chance that the kidney will be deemed unsuitable for transplantation and the transplant procedure will not go ahead. Each patient will be followed up for 3 months post-transplant. Follow up involves normal clinical visits at least twice a week for six weeks and then weekly for a further six weeks. At three months after the transplant we will plan to perform a routine needle biopsy of the kidney to look for scarring. This would help us with our research but it is not compulsory. Needle biopsies have a good safety record but there is a small risk (less than 1%) of significant bleeding.
Intervention type	Other
Primary outcome measure(s)	Graft function after transplantation is assessed by measuring serum creatinine levels over the first seven days post-transplant then one and three months after transplantation.
Key secondary outcome measure(s)	1. Rates of delayed graft function (DGF), defined as the need for dialysis within the first 7 days after transplant. Episodes of dialysis will be recorded and the need for dialysis assessed by measuring levels of creatinine in the blood. Samples will be taken daily 2. Slow graft function rate (SGF), defined as a less than 10% reduction in serum creatinine levels within for 3 consecutive days after transplantation, is measured using serum creatinine levels in the blood. Samples will be taken daily for 7 days post-transplant. 3. Rates of primary non function (PNF), defined as the graft never functioning, is measured using levels of creatinine in the blood. 4. Episodes of acute rejection within the first 3 months are diagnosed by taking a tissue sample from the kidney. 5. Adverse reactions e.g. infection, thrombosis of the graft will be recorded 6. Length of hospital stay is measured by calculating the number of days the patient remains in hospital after the transplant 7. Perfusion parameters during perfusion of the kidney (renal blood flow, urine output) 8. Histopathology, molecular markers measured in tissue samples taken from the kidney before after the transplant will be performed during the transplant procedure 9. Quality of life is measured using the Kidney disease Quality of Life – short form at baseline (before transplant) and 3 months post-transplant Long-term secondary outcomes: 1. Graft function after transplantation is assessed by measuring serum creatinine levels at 6 and 12 months 2. Renal function is measured by determining eGFR levels at 6 and 12 months 3. Number of rejection episodes is diagnosed by taking a tissue sample from the kidney over 12 months 4. Incidences of graft loss is measured by recording the failure of the graft over 12 months
Completion date	04/11/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	90
Total final enrolment	21
Key inclusion criteria	1. Kidneys declined for transplantation by several transplant centres and by all the fast-track transplant centres due to adverse donor characteristics, prolonged ischaemia, gross appearance, histological changes (excluding cancer), and cold perfusion parameters. 2. Donor and recipient age ≥ 18 years 3. Patient undergoing a 1st or 2nd renal transplant from a deceased donor 4. Written, signed informed consent to the procedure
Key exclusion criteria	1: Kidneys that are deemed unsuitable for transplantation due to contraindications defined by current NHSBT criteria . 2: Kidneys with irreparable vascular damage. 3: Recipients of a 3rd or subsequent transplant.
Date of first enrolment	21/12/2015
Date of final enrolment	01/11/2019

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Addenbrooke’s Hospital

Hill’s Road
Cambridge
CB2 OQQ
United Kingdom

Guy’s Hospital

Great Maze Pond
London
SE1 9RT
United Kingdom

Freemans Hospital

Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	case report	07/06/2016	09/09/2021	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 17	16/03/2015	26/08/2022	No	No

Additional files

32116 Protocol version 17 16March2015.pdf: Protocol file

Editorial Notes

26/08/2022: Uploaded protocol (not peer-reviewed) as an additional file.
09/09/2021: The following changes have been made:
1. Publication reference added.
2. The overall trial end date has been changed from 31/03/2020 to 04/11/2020 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 31/03/2021 to 30/11/2021.
4. The total final enrolment number has been added.
02/04/2019: The condition has been changed from "Specialty: Renal disorders, Primary sub-specialty: Renal disorders" to "Kidney transplantation" following a request from the NIHR.