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. 2019 Jan;19(1):178-192.
doi: 10.1111/ajt.14932. Epub 2018 Jun 20.

Twenty-four-hour normothermic perfusion of discarded human kidneys with urine recirculation

Annemarie Weissenbacher  1 , Letizia Lo Faro  1 , Olga Boubriak  2 , Maria F Soares  3 , Ian S Roberts  3 , James P Hunter  1 , Daniel Voyce  4 , Nikolay Mikov  4 , Andrew Cook  4 , Rutger J Ploeg  1 , Constantin C Coussios  2 , Peter J Friend  1
Affiliations

Twenty-four-hour normothermic perfusion of discarded human kidneys with urine recirculation

Annemarie Weissenbacher et al. Am J Transplant. 2019 Jan.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Am J Transplant. 2021 Apr;21(4):1675. doi: 10.1111/ajt.16521. Am J Transplant. 2021. PMID: 33788995 Free PMC article. No abstract available.

Abstract

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) and 5 being from donors after circulatory death (36.2 ± 38.3 hours). Three kidneys were perfused using Ringer's lactate to replace excreted urine volume, and 8 kidneys were perfused using urine recirculation to maintain perfusate volume without fluid replenishment. In all cases, normothermic perfusion either maintained or slightly improved the histopathologically assessed tubular condition, and there was effective urine production in kidneys from both donors after brain death and donors after circulatory death (2367 ± 1798 mL vs 744.4 ± 198.4 mL, respectively; P = .44). Biomarkers, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were successfully detected and quantified in the perfusate. All kidneys with urine recirculation were readily perfused for 24 hours (n = 8) and exhibited physiological perfusate sodium levels (140.7 ± 1.2 mmol/L), while kidneys without urine recirculation (n = 3) achieved a reduced normothermic perfusion time of 7.7 ± 1.5 hours and significantly higher perfusate sodium levels (159.6 ± 4.63 mmol/:, P < .01). Normothermic machine perfusion of human kidneys for 24 hours appears to be feasible, and urine recirculation was found to facilitate the maintenance of perfusate volume and homeostasis.

Keywords: clinical research/practice; kidney (native) function/dysfunction; kidney transplantation/nephrology; organ perfusion and preservation; translational research/science.

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Figures

Figure 1
Figure 1
A. Diagram/schematic drawing of the prototype device for long‐term normothermic kidney perfusion: (1) Kidney. (2) Organ container, including perforated kidney sling. (3) Arterial cannula at kidney inlet. (4) Venous cannula at kidney outlet. (5) Ureter outlet duct. (6) Urine flow meter. (7) Duct for recirculation of fluids leaked by the kidney. (8) Soft‐shell reservoir. (9) Perfusion pump (centrifugal pump). (10) Oxygenator & heat exchanger. (11) Heat exchanger water inlet. (12) Heat exchanger water outlet. (13) Proportional pinch valve (capable of both fixed & alternating constriction). (14) In line blood gas analysis sensor capable of measuring temperature, po 2, pco 2, pH. (15) Ultrasonic arterial flow meter. (16) Arterial pressure gauge. 17 Venous pressure gauge. (18) Syringe pump. B. Prototype device for long‐term normothermic kidney perfusion (OrganOx Ltd, Oxford, UK) [Color figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
A. Kidney 3 after 24 hours of normothermic perfusion. B. Prototype device in operation mode. (1) Organ container with kidney. (2) Soft‐shell reservoir. (3) Perfusion pump (centrifugal pump). (4) Oxygenator & heat exchanger. (5) Urine recirculation line [Color figure can be viewed at wileyonlinelibrary.com]
Figure 3
Figure 3
A. Arterial flow values in mL/min per kidney with urine recirculation over time. B. Arterial flow values in mL/min per kidney without urine recirculation over time. C. Intrarenal resistance values in mm Hg/mL/min per kidney with urine recirculation over time. D. Intrarenal resistance values in mm Hg/mL/min per kidney without urine recirculation over time
Figure 4
Figure 4
A. pH values per kidney with urine recirculation during 24 hours of normothermic perfusion. B. pH values per kidney without urine recirculation during 24 hours of normothermic perfusion
Figure 5
Figure 5
A. Urine flow: Hourly amounts per kidney during 24 hours of normothermic perfusion. B. Urine flow: Hourly amounts per kidney without urine recirculation during normothermic perfusion
Figure 6
Figure 6
Histology photographs. A. Zero biopsy kidney 8. B. Biopsy after 24 hours of normothermic perfusion kidney 8. C. Zero biopsy kidney 11. D. Biopsy after 8 hours of normothermic perfusion kidney 11 [Color figure can be viewed at wileyonlinelibrary.com]
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