Normothermic Machine Perfusion (NMP) Versus Hypothermic Machine Perfusion (HMP) in Human Kidney Transplantation

Not Applicable

Not yet recruiting

• Conditions: Kidney Transplantation
• Interventions: Device: Normothermic machine perfusion; Device: Hypothermic machine perfusion

• Registration Number: NCT05743751
• Lead Sponsor: Zhang Tianyu

Brief Summary

Due to the rising incidence of renal failure and the improvement of organ transplantation technology, the shortage of donor organs has become one of the main problems limiting the development of kidney transplantation. Marginal donor is one of the important ways to extend the donor pool. Normothermic mechanical perfusion (NMP) is a new generation of organ preservation technology, which can maintain the blood supply and at the same time evaluate the marginal kidney function during the organ preservation. However, the clinical effect has not been proved. Hypothermic Machine Perfusion (HMP) is the mainstream organ perfusion technology. This study aims to compare the effectiveness of NMP with the HMP.

Detailed Description

The main purpose of the study is to improve the utilization rate of marginal donors through normothermic perfusion, and reduce the incidence of infection, severe rejection and even graft failure caused by implantation of marginal donors. This study aims at the following aspects:

1. To compare the effects of two methods and perfusion parameters on the quality of marginal donors: normal temperature pulse perfusion and low temperature mechanical perfusion;

2. Explore the methods of evaluating the function of donor organs;

3. Exploring the effects of different mechanical perfusion methods and perfusion conditions on marginal donors;

4. The effect of broad-spectrum antibiotics on improving donor infection through different administration routes and different drug doses during perfusion and preservation.

A single-center prospective randomized controlled study was used to compare the prognosis of renal transplantation between 50 patients with normothermic pulse perfusion and 50 patients with hypothermic mechanical perfusion who were enrolled in our hospital for allograft kidney transplantation.

Assessment factors:

1. Donor parameters: age, sex, creatinine, diabetes, cause of death, length of stay in ICU, calcification of donor renal artery (CRP expression level)

2. Perfusion pressure, perfusion time, perfusion temperature, perfusion vessel resistance index

3. Receptor factors: age, gender, height, weight, BMI, cause of kidney disease (hypertension, diabetes glomerulonephritis, polycystic kidney disease), dialysis time (month), dialysis type (blood/peritoneum), HLA mismatch number, smoking, diabetes, hypertension, heart disease, hyperlipidemia, anemia, complication index (CCI), ASA score (\>3 or ≤ 3), operation time, number of donor renal artery branches, number of donor renal vein branches, donor creatinine, cold ischemia time (mins), and the perfusion of the transplanted kidney ( judged by the fluorescence intensity after indocyanine green injection). Laboratory results: PRA (panel-reactive antibody), blood creatinine, estimated glomerular filtration rate (eGFR), blood lactate level, postoperative urine volume. Graft loss, culture result of irrigation solution (bacteria). Sample acquisition: obtaining the blood and urine samples of the recipient and measuring the expression level of globulin A in the serum. In the process of kidney transplantation, the donor's renal artery vessel wall and the recipient's external iliac artery vessel wall were obtained. The blood vessel wall was stained with calcification, CRP to evaluate the calcification of the donor and recipient vessels.

Study Timeline

• Study First Submitted: 2023-01-28
• Status Verified: 2023-02
• Study First Submitted QC: 2023-02-14
• Last Update Submitted: 2023-02-14
• Study First Posted: 2023-02-24
• Last Update Posted: 2023-02-24
• Study Start: 2023-03-03
• Primary Completion: 2024-12-03
• Study Completion: 2025-09-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age 18-60 years old, gender unlimited

• Volunteer to participate in this clinical trial and sign the informed consent form

• Suffering from end-stage renal disease

• Planned kidney transplantation

• The expanded standard donors (ECD) were obtained

  • The expanded standard kidney donor is defined as: aged cadaver donors over 60 years old or two or three of the following conditions between 50 and 60 years old: death due to cerebrovascular disease; Hypertension; The blood creatinine level before donation was greater than 133umol/L.

Exclusion Criteria

• Active infection
• Living donor kidney recipient
• Acute rejection
• Second kidney transplantation
• Combined transplantation (combined liver and kidney, combined pancreas and kidney)
• Patients who take other clinical trial drugs or participate in other clinical studies
• Unable to continue the research
• Patients who are judged by the researcher to be unsuitable for this clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normothermic machine perfusion	Normothermic machine perfusion	After conventional UW perfusion is obtained, the marginal donor kidney is immediately perfused without ischemia at normal temperature. The perfusion time is at least 4 hours (so as to repair the marginal donor kidney). The perfusion solution is as above, and the perfusion solution is loaded into the device authorized in Europe (XVIVO - KidneyAssist ®）， Connect the transplanted renal artery with the device. Take 5ml perfusion solution in advance before perfusion, 5ml perfusion solution every 30min after perfusion, take perfusion solution at the end of perfusion (blood gas analysis for each perfusion solution, and finally perfusion solution for culture), and measure urine volume every hour. After perfusion, the transplanted kidney was disconnected from the perfusion device, and the donor kidney was perfused again with 2L HTK solution, followed by routine transplantation.
Hypothermic machine perfusion	Hypothermic machine perfusion	After organ acquisition, the donor kidney was trimmed, and then the donor kidney was connected to the cryoperfusion machine (lifeport, which has been used in routine clinical practice in our hospital) for continuous low temperature mechanical perfusion (\<8 ℃). The perfusion solution was extracted for proteomic study at 10 min after perfusion and at the end of perfusion.

Primary Outcome Measures

Name	Time	Method
Rate of delayed renal function (DGF)	1 week after surgery	At least one dialysis is required within one week after kidney transplantation

Secondary Outcome Measures

Name	Time	Method
Estimated glomerular filtration rate	3, 6, 12 months after surgery	Calculated from serum creatinine levels to assess kidney function.
Rate of primary non-function (PNF)	1 months after surgery	Dialysis is required because the transplanted kidney is nonfunctional
Graft survival and recipient survival	1 year follow-up	Incidence of the Graft survival and recipient survival
Complications	within 90 days after operation	incidence of complications
Patient death	1 year follow-up	Death date after surgery and the reasons

Trial Locations

Locations (1)

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China