Development of a score for quality assessment of deceased donor kidneys in Eurotransplant

• Applicant: Privatdozent Dr. Jan Ulrich Becker
• Subject Area: Nephrology ; General and Visceral Surgery ; Pathology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409150529

• Final Report Year: 2024

Final Report Abstract

In Germany, waiting times for a deceased donor kidney is too long for patients on dialysis, with negative effects not only their well-being but also their survival. The distribution and allocation of kidney transplants from deceased donors is handled for Germany by Eurotransplant. To mitigate the scarcity of deceased donor kidneys, kidneys of decreasing quality from increasingly older patients with cardiovascular morbidity are offered. Such donor kidneys of inferior quality potentially endanger the wellbeing and the survival of the recipient. Exact scores for the prediction of delayed graft function and transplant loss within the first year and thus the quality of the donor kidney are crucial to better exploit the scarce pool of donor kidneys without endangering the recipients. With this project, we have fulfilled this need by designing two scores for the prediction of such negative outcomes: 2-Step-DGF for delayed graft function and 2-Step-1y for transplant loss within the first year. Both these scores have a novel design, with optional histology. Histology is often not necessary for the prediction and delays transplantation which by itself decreases the organ quality. Apart from this innovative design with optional histology, our scores are designed to be updateable for new scenarios, other countries and the future in Eurotransplant with relative ease due to their modular design. Moreover, during the course of this project, we have created additional datasets which allowed us to show the insufficient performance of previous scores for the Eurotransplant environment; we could challenge the decision for non-acceptance in a dataset of discarded donor kidneys; we could examine the correlation of the kinetics of the kidney function marker creatine before explantation with function after transplantation. The project lead could contribute to the consensus about procurement biopsy diagnostics organized by the European Society of Organ Transplantation. Another legacy of this project is a public granular clinicopathological dataset of pre-transplant biopsies under the custody of Eurotranplant. Furthermore, we could compile a set of 450 procurement biopsies from Northern Italy (Padova, Verona, Bologna). Both datasets are currently being used to establish scores for the prediction of delayed graft function and 1-year transplant loss with multimodal machine learning models. For this topic, the project lead and the Italian collaborators have published three opinion pieces. These combined datasets are also being used on an internally funded project at the University of Cologne to establish Meta-Scores for both delayed graft function and 1- year transplant loss, using our novel 2-Step design with optional histology.

Publications

• Effect of creatinine metrics on outcome after transplantation of marginal donor kidneys. Nephrology, 27(12), 973-982.
  Scurt, Florian G.; Ernst, Angela; Hammoud, Ben; Wassermann, Tamara; Mertens, Peter R.; Schwarz, Anke; Becker, Jan U. & Chatzikyrkou, Christos
  
• Short-term outcomes after transplantation of deceased donor kidneys with acute kidney injury: a retrospective analysis of a multicenter cohort of marginal donor kidneys with post-explantation biopsies. International Urology and Nephrology, 55(1), 115-127.
  Scurt, Florian G.; Ernst, Angela; Wassermann, Tamara; Hammoud, Ben; Mertens, Peter R.; Schwarz, Anke; Becker, Jan U. & Chatzikyrkou, Christos
  
• European Society for Organ Transplantation (ESOT)-TLJ 3.0 Consensus on Histopathological Analysis of Pre-Implantation Donor Kidney Biopsy: Redefining the Role in the Process of Graft Assessment. Transplant International, 36.
  Zaza, Gianluigi; Cucchiari, David; Becker, Jan Ulrich; de Vries, Aiko P. J.; Eccher, Albino; Florquin, Sandrine; Kers, Jesper; Rabant, Marion; Rossini, Michele; Pengel, Liset; Marson, Lorna & Furian, Lucrezia
  
• Performance of Scores Predicting Adverse Outcomes in Procurement Kidney Biopsies From Deceased Donors With Organs of Lower-Than-Average Quality. Transplant International, 36.
  Scurt, Florian G.; Ernst, Angela; FischerFröhlich, Carl-Ludwig; Schwarz, Anke; Becker, Jan U. & Chatzikyrkou, Christos
  
• Pre-Implantation Kidney Biopsies in Extended Criteria Donors: From On Call to Expert Pathologist, from Conventional Microscope to Digital Pathology. Critical Reviews™ in Oncogenesis, 28(3), 7-20.
  Marletta, Stefano; Di Bella, Caterina; Catalano, Giovanni; Mastrosimini, Maria Gaia; Becker, Jan; Ernst, Angela; Rizzo, Paola Chiara; Caldonazzi, Nicolo; Vasuri, Francesco; Malvi, Deborah; Fanelli, Giuseppe Nicolo; Naccarato, Giuseppe; Ghimenton, Claudio; L.'Imperio, Vincenzo; Mescoli, Claudia; Eccher, Albino; Furian, Lucrezia & Pagni, Fabio
  
• 2-Step Scores with optional nephropathology for the prediction of adverse outcomes for brain-dead donor kidneys in Eurotransplant. Nephrology Dialysis Transplantation, 40(1), 83-108.
  Ernst, Angela; Regele, Heinz; Chatzikyrkou, Christos; Dendooven, Amélie; Turkevi-Nagy, Sándor; Tieken, Ineke; Oberbauer, Rainer; Reindl-Schwaighofer, Roman; Abramowicz, Daniel; Hellemans, Rachel; Massart, Annick; Ljubanovic, Danica Galesic; Senjug, Petar; Maksimovic, Bojana; Aßfalg, Volker; Neretljak, Ivan; Schleicher, Christina; Clahsen-van, Groningen Marian; Kojc, Nika ... & Becker, Jan U.
  
• The Puzzle of Preimplantation Kidney Biopsy Decision-Making Process: The Pathologist Perspective. Life, 14(2), 254.
  Eccher, Albino; Becker, Jan Ulrich; Pagni, Fabio; Cazzaniga, Giorgio; Rossi, Mattia; Gambaro, Giovanni; L.’Imperio, Vincenzo & Marletta, Stefano