normothermic preservation of a kidney graft from uncontrolled donation after circulatory death over 73 hours.

Journal: Frontiers in bioengineering and biotechnology
Published Date:

Abstract

The transplant community is focused on prolonging the preservation time of kidney grafts to allow for long-distance kidney graft transportation, assess the viability of marginal grafts, and optimize a platform for the translation of innovative therapeutics to clinical practice, especially those focused on cell and vector delivery to organ conditioning and reprogramming. We describe the first case of feasible preservation of a kidney from a donor after uncontrolled circulatory death over a 73-h period using normothermic perfusion and analyze hemodynamic, biochemical, histological, and transcriptomic parameters for inflammation and kidney injury. The mean pressure and flow values were 71.24 ± 9.62 mmHg and 99.65 ± 18.54 mL/min, respectively. The temperature range was 36.7°C-37.2°C. The renal resistance index was 0.75 ± 0.15 mmHg/mL/min. The mean pH was 7.29 ± 0.15. The lactate concentration peak increased until 213 mg/dL at 6 h, reaching normal values after 34 h of perfusion (8.92 mg/dL). The total urine output at the end of perfusion was 1.185 mL. Histological analysis revealed no significant increase in acute tubular necrosis (ATN) severity as perfusion progressed. The expression of KIM-1, VEGF, and TGFβ decreased after 6-18 h of perfusion until 60 h in which the expression of these genes increased again together with the expression of -catenin, Ki67, and TIMP1. We show that normothermic perfusion can maintain a kidney graft viable for 3 days, thus allowing a rapid translation of pre-clinical therapeutics to clinical practice.

Authors

  • Enrique Montagud-Marrahi
    Kidney Transplant Unit. Nephrology and Kidney Transplantation Department. Hospital Clinic of Barcelona, Barcelona, Spain.
  • Yosu Luque
    Sorbonne Université - Inserm UMRS_1155, Paris, France.
  • Ruben Rabadan Ros
    Group of Metabolism and Genetic Regulation of Disease, UCAM HiTech Sport & Health Innovation Hub, Universidad Católica de Murcia, Guadalupe, Spain.
  • Tarek Ajami
    Kidney Transplant Unit. Urology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Elena Cuadrado-Payan
    Kidney Transplant Unit. Nephrology and Kidney Transplantation Department. Hospital Clinic of Barcelona, Barcelona, Spain.
  • Hector Estrella
    Kidney Transplant Unit. Urology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Andres Arancibia
    Kidney Transplant Unit. Urology Department, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Gerard Sánchez-Etayo
    Donation and Transplant Coordination Section, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • Marc Bohils
    Donation and Transplant Coordination Section, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • Ramsés Marrero
    Donation and Transplant Coordination Section, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • Yilliam Fundora
    Liver Transplant Unit, Institut Clínic de Malalties Digestives I Metabòliques, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Maria José Ramírez-Bajo
    Laboratori Experimental de Nefrologia i Trasplantament (LENIT). Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Elisenda Banon-Maneus
    Laboratori Experimental de Nefrologia i Trasplantament (LENIT). Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Jordi Rovira
    Laboratori Experimental de Nefrologia i Trasplantament (LENIT). Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Ana-Belén Larque
    Department of Pathology. Hospital Clinic of Barcelona. Corresponding Author: Mireia Musquera, Barcelona, Spain.
  • Josep Maria Campistol
    Kidney Transplant Unit. Nephrology and Kidney Transplantation Department. Hospital Clinic of Barcelona, Barcelona, Spain.
  • Fritz Diekmann
    Kidney Transplant Unit. Nephrology and Kidney Transplantation Department. Hospital Clinic of Barcelona, Barcelona, Spain.
  • Mireia Musquera
    Kidney Transplant Unit. Urology Department, Hospital Clinic of Barcelona, Barcelona, Spain.

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