Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion

Peter Urbanellis, MD, MSc; Dagmar Kollmann, MD, PhD; Ivan Linares, MD, PhD; Sujani Ganesh, MSc; Fabiola Oquendo, MD; Laura Mazilescu, MD; Toru Goto, MD; Yuki Noguchi, MD, PhD; Rohan John, MD; Ana Konvalinka, MD, PhD; Istvan Mucsi, MD, PhD; Anand Ghanekar, MD, PhD; Darius Bagli, MD; Markus Selzner, MD; Lisa A. Robinson, MD

doi:10.1097/TXD.0000000000001030

Transplantation Direct (Aug 2020)

Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion

Peter Urbanellis, MD, MSc,
Dagmar Kollmann, MD, PhD,
Ivan Linares, MD, PhD,
Sujani Ganesh, MSc,
Fabiola Oquendo, MD,
Laura Mazilescu, MD,
Toru Goto, MD,
Yuki Noguchi, MD, PhD,
Rohan John, MD,
Ana Konvalinka, MD, PhD,
Istvan Mucsi, MD, PhD,
Anand Ghanekar, MD, PhD,
Darius Bagli, MD,
Markus Selzner, MD,
Lisa A. Robinson, MD

Affiliations

Peter Urbanellis, MD, MSc: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Dagmar Kollmann, MD, PhD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Ivan Linares, MD, PhD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Sujani Ganesh, MSc: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Fabiola Oquendo, MD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Laura Mazilescu, MD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Toru Goto, MD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Yuki Noguchi, MD, PhD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Rohan John, MD: 5 Laboratory Medicine and Pathobiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Ana Konvalinka, MD, PhD: 2 Canadian Donation and Transplantation Research Program, Edmonton, Alberta, Canada.
Istvan Mucsi, MD, PhD: 2 Canadian Donation and Transplantation Research Program, Edmonton, Alberta, Canada.
Anand Ghanekar, MD, PhD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Darius Bagli, MD: 7 Departments of Surgery (Urology) & Physiology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Markus Selzner, MD: 1 Multi-Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Lisa A. Robinson, MD: 3 Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

DOI: https://doi.org/10.1097/TXD.0000000000001030
Journal volume & issue: Vol. 6, no. 8
p. e587

Abstract

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Background. Normothermic ex vivo kidney perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could improve early function of severely injured grafts and reduce the incidence of significant renal dysfunction (SRD) similar to delayed graft function in a model of donation after circulatory death. Methods. Kidneys from 30-kg Yorkshire pigs were removed following 120 minutes of warm ischemia (WI). These grafts were then preserved in static cold storage (SCS, n = 6) or subjected to NEVKP (n = 5) for 8 hours before heterotopic autotransplantation. SRD was defined as postoperative day (POD) 4 oliguria 6.0 mmol/L. Results. All 4 surviving animals with 120 minutes WI grafts stored with SCS developed SRD, compared with 1/5 in the NEVKP group (P = 0.02). The NEVKP group, when compared with SCS, also demonstrated significantly decreased serum creatinine peak values (1118.51 ± 206.90 µmol/L versus 1675.56 ± 98.15 µmol/L; P = 0.002) and higher creatinine clearance (POD4: 9.05 ± 6.97 mL/min versus 0.89 ± 0.56 mL/min; P = 0.05). By POD7, serum creatinine was not significantly different than baseline in the NEVKP (431.49 ± 492.50 µmol/L versus 90.19 ± 14.15 µmol/L, respectively; P = 0.20) but remained elevated following SCS (1189.25 ± 309.47 µmol/L versus 97.26 ± 29.18 µmol/L, respectively; P < 0.01). Histology demonstrated significantly decreased tubular injury scores compared with SCS grafts (P = 0.03). Conclusions. Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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