PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration

Not Applicable

• Conditions: End Stage Renal Disease
• Interventions: Procedure: Prolonged normothermic machine perfusion

• Registration Number: NCT04693325
• Lead Sponsor: Leiden University Medical Center

Brief Summary

The investigators would like to introduce and clinically evaluate prolonged normothermic machine perfusion (PNMP) to preserve and assess high-risk donor kidneys prior to transplantation.

Detailed Description

Currently kidney transplantation is the only viable option for patients with kidney failure to regain quality of life and health. The number of organs available for transplantation is insufficient with a widening gap between supply and demand. Nowadays, centers accept older and higher risk donor organs with co-morbidity, often leading to non-function, complications and with half of the patients back on dialysis within 15 years. Furthermore, many donor kidneys have to be discarded as too damaged and beyond repair. Increasing the quality and therefore transplantability of these high-risk donor organs could significantly increase the donor kidney pool.

Using prolonged normothermic perfusion of marginal donor organs, the investigators aim to kick start regeneration in the kidney before transplantation, improving function and survival long-term. Furthermore, the choice to accept or decline a donor kidney organ is currently based on subjective criteria and causes great uncertainty amongst clinicians. There is a dire need for tools to aid in decision making and reduce this uncertainty. Biomarkers predictive of graft regeneration are lacking. Samples from perfused kidneys and donor recipients will be collected and analysed to allow the formulation of a kidney fitness index.

Study Timeline

• Study First Submitted: 2020-06-24
• Study First Submitted QC: 2020-12-30
• Study First Posted: 2021-01-05
• Status Verified: 2021-12
• Study Start: 2021-12-01
• Last Update Submitted: 2021-12-13
• Last Update Posted: 2022-01-03
• Primary Completion: 2022-07
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Patients undergoing 1st or 2nd kidney transplant
• Patients undergoing a kidney transplantation from DCD Maastricht III & V
• Transplant recipients aged ≥ 18 years
• Written informed consent

Exclusion Criteria

• Patients undergoing 3rd or subsequent kidney transplant
• Patients undergoing a kidney transplantation from DCD Maastricht I, II & IV
• Transplant recipients aged < 18 years
• Patients receiving multi-organ transplants
• ABO/HLA incompatible transplants
• Highly sensitized patients with a panel-reactive antibody (PRA) ≥85%
• Kidneys with CIT > 12 hrs at the point of arrival at transplant centre
• Kidneys with complex vascular anatomy (≥3 arteries, artery which cannot be can-nulated or attached to the patch holder)
• Kidneys explanted from a donor on normothermic regional perfusion

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Prolonged normothermic machina perfusion	Prolonged normothermic machine perfusion	Eligible and consenting patients who will receive a donor kidney will be included for participation in this study. Current practice is to preserve donor kidneys on hypothermic machine perfusion (HMP). In this study, donor kidneys (n=18) will be taken off the HMP after arrival in the transplant center. These will then be perfused with oxygenated perfusate using the NMP device following an optimised NMP protocol.

Primary Outcome Measures

Name	Time	Method
glomerular filtration rate (GFR)	6 months post transplantation	renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Secondary Outcome Measures

Name	Time	Method
primary non-function	6 months post transplantation	defined as permanent lack of graft function from the time of transplantation, was diagnosed when a kidney graft was well perfused (confirmed by ultrasound examination) but never functioned, necessitating dialysis after kidney transplantation
delayed graft function (DGF)	6 months post transplantation	defined as the need for postoperative dialysis during the first 7 days after transplantation
patient and graft survival	6 months post transplantation	time from transplant to patient death, and graft failure
glomerular filtration rate (GFR)	3 months post transplantation	renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
adverse events	6 months post transplantation	defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the normothermic machine perfusion of the donor kidney prior to transplantation
postoperative complications	6 months post transplantation	graded according to the comprehensive complication index

Trial Locations

Locations (2)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands