Pulsed Perfusion for Marginal Kidneys (PREDICTION)

A PROSPECTIVE STUDY TO COMPARE EARLY GRAFT FUNCTION OF RECIPIENTS OF SINGLE OR DUAL KIDNEY ORGANS STORED IN ICE COLD SOLUTION OR PULSED PERFUSION

Trends in organ donor pool are characterized by an increasing age and a shift towards cerebrovascular diseases as primary causes of death. As a result, donors older than 60 years nowadays represent more than one fourth of the entire donor pool in Italy. This, along with an increasing number of patients on the waiting list for transplantation, prompted a growing use of organs from subjects older than 60 years that would have been considered unsuitable years ago. To improve graft outcomes, transplant of two older kidneys in the same recipient has been proposed. To optimize allocation of these organs to single or dual transplantation,a scoring system for kidneys, based on biopsy, with scores ranging from a minimum of 0 (indicating the absence of renal lesions) to a maximum of 12 (indicating the presence of marked changes in the renal parenchyma) has been suggested. According to this panel, kidneys with a score of 4 or lower are predicted to contain enough viable nephrons to be used as single transplants, those with a score of 5, 6, or 7 can be used as dual transplants, kidneys with a score greater than 7 are discarded. The survival of kidney grafts obtained from donors older than 60 years and allocated for single or dual transplantation on the basis of biopsy findings before transplantation was similar to that of single grafts from younger donors. To further improve these results, set-up of strategies to preserve organs is crucial to save the residual nephron mass and optimize outcomes of these marginal grafts. In this regard, over the past 30 years two methods of kidney preservation have been developed. With cold storage, the kidney is flushed once it is removed from the donor and placed in an ice-cooled container with preservation solution. With the use of pulsatile machine perfusion, the kidney is connected to a machine, which pumps a cold solution containing oxygen and nutrients through the kidney. This process allows for metabolism to continue in the kidney with end products being removed. The broad aim of the present study is to evaluate whether pulsatile machine perfusion of kidneys from older/marginal donors may provide better outcomes than static perfusion. To this purpose the outcome of recipients of perfused kidneys will be compared with the outcome of historical controls receiving non-perfused kidney selected and allocated on the basis of the same criteria and matched by gender, age and kidney histologic score.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Procedure: Kidney perfused by pulsatile machine; Procedure: Storage of kidney in refrigerated solution

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24100
    • A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/U.O. Chirurgia Pediatrica
  • Pavia, Italy, 27100
    • IRCCS Policlinico S.Matteo - UOS trapianto di Rene/U.O. Nefrologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who are eligible to receive a single or dual transplant from older/marginal deceased donors identified according to the Nord Italia Transplant criteria who consent to receive perfused with a pulsatile machine.

Description

Inclusion Criteria:

• Males and females aged 50 years or more and no more than 10 years older or younger than their corresponding donors;
• First single or double kidney transplant from deceased donors older than 60 years;
• Pre-implantation histologic evaluation and graft selection and allocation based on the histologic score and according to the Nord Italian Transplant (NIT) criteria;
• Written informed consent.

Exclusion Criteria:

• Any factor that according to the NIT selection criteria represent a contraindication to receive a deceased donor kidney transplant
• Need for specific de-sensitization protocols because of high immunological risk (according to NIT criteria) or participation in other concomitant intervention studies
• Vascular abnormalities/changes that preclude the possibility to perfuse the kidney grafts by a pulsatile machine

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Kidney perfused by pulsatile machine	Procedure: Kidney perfused by pulsatile machine
Kidney stored in refrigerated solution	Procedure: Storage of kidney in refrigerated solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glomerular filtration rate (GFR)		6 months after transplant.
Renal resistance	Renal resistance is measured by graft ultrasound. It ranges from 0 to 1.	6 hours after pulsatile machine perfusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between renal resistance measured at 6 hours after machine perfusion and renal histological score at pre-transplant biopsy	The severity of changes in kidney at pre-transplant biopsy was quantified by a predefined histologic score. Changes in each evaluated component of the kidney tissue , vessels, glomeruli, tubules, and connective tissue, received a score ranging from 0 to 3. The sum of these scores was defined as the global kidney score, which could range from 0 to 12. Renal resistance is measured by graft ultrasound. It ranges from 0 to 1.	6 hours after pulsatile machine perfusion
Correlation between renal resistances measured at 6 hours after pulsatile machine perfusion and intergraft resistances measured by ultrasound at 7 days and 6 months after transplant.	Renal resistances are measured by graft ultrasound. They range from 0 to 1.	Changes from 7 days at 6 months after transplant .
Incidence of delayed graft function (DGF).		Within the first week after transplant

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: Fondazione IRCCS Policlinico San Matteo di Pavia
• Investigators: Study Chair: Paolo Cravedi, MD, IRCCS - Mario Negri Institute for Pharmacological Research; Principal Investigator: Giuseppe Remuzzi, MD, IRCCS - istituto di Ricerche Farmacologiche Mario Negri - A.O. Papa Giovanni XXIII BG; Principal Investigator: Giovanni Rota, MD, A.O. Papa Giovanni XXIII, Bergamo, Italy - U.O. Chirurgia Pediatrica; Principal Investigator: Salvatore De Pascale, MD, A.O. Papa Giovanni XXIII, Bergamo, Italy - U.O. Chirurgia Pediatrica; Principal Investigator: Francesco La Canna, MD, A.O. Papa Giovanni XXIII, Bergamo, Italy - U.O. Chirurgia Pediatrica; Principal Investigator: Giuseppe Piccolo, MD, NIT (North Italian Transplant); Principal Investigator: Giuseppe Rossini, MD, NIT (North Italian Transplant); Principal Investigator: Sergio Vesconi, MD, NIT (North Italian Transplant)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: January 28, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Kidney transplant; Graft function; Marginal donors; Pulse perfusion
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: PREDICTION