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. 2019 Feb;103(2):392-400.
doi: 10.1097/TP.0000000000002299.

Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation

Sandra K Kabagambe  1 , Ivonne P Palma  1 , Yulia Smolin  1 , Tristan Boyer  1 , Ivania Palma  1 , Junichiro Sageshima  1 , Christoph Troppmann  1 , Chandrasekar Santhanakrishnan  1 , John P McVicar  1 , Kuang-Yu Jen  2 , Miriam Nuño  3 , Richard V Perez  1
Affiliations

Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-risk Deceased Donor Human Kidneys for Transplantation

Sandra K Kabagambe et al. Transplantation. 2019 Feb.

Abstract

Background: Despite careful clinical examination, procurement biopsy and assessment on hypothermic machine perfusion, a significant number of potentially useable deceased donor kidneys will be discarded because they are deemed unsuitable for transplantation. Ex vivo normothermic perfusion (EVNP) may be useful as a means to further assess high-risk kidneys to determine suitability for transplantation.

Methods: From June 2014 to October 2015, 7 kidneys (mean donor age, 54.3 years and Kidney Donor Profile Index, 79%) that were initially procured with the intention to transplant were discarded based on a combination of clinical findings, suboptimal biopsies, long cold ischemia time (CIT) and/or poor hypothermic perfusion parameters. They were subsequently placed on EVNP using oxygenated packed red blood cells and supplemental nutrition for a period of 3 hours. Continuous hemodynamic and functional parameters were assessed.

Results: After a mean CIT of 43.7 hours, all 7 kidneys appeared viable on EVNP with progressively increasing renal blood flow over the 3-hour period of perfusion. Five of the 7 kidneys had excellent macroscopic appearance, rapid increase in blood flow to 200 to 250 mL/min, urine output of 40 to 260 mL/h and increasing creatinine clearance.

Conclusions: Favorable perfusion characteristics and immediate function after a 3-hour course of EVNP suggests that high-risk kidneys subjected to long CIT may have been considered for transplantation. The combined use of ex vivo hypothermic and normothermic perfusion may be a useful strategy to more adequately assess and preserve high-risk kidneys deemed unsuitable for transplantation. A clinical trial will be necessary to validate the usefulness of this approach.

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Conflict of interest statement

R.V.P. is a member of the clinical advisory board for XOR Laboratories, Toronto, Canada. All the other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Ex vivo normothermic perfusion circuit. After priming the circuit, the perfusate flows into the kidney via renal arterial cannula. Venous blood passively flows from the renal vein into a reservoir. A centrifugal pump circulates the venous perfusate to the oxygenator and heater/cooler. Flow and pressure probes are used to adjust and maintain mean arterial pressure at 70 to 80 mm Hg. The perfusate returns to the kidney via the renal arterial cannula. Urine is collected into a beaker via a ureteral catheter.
FIGURE 2
FIGURE 2
Pictures of kidneys before and during ex vivo normothermic perfusion (EVNP). Although their macroscopic appearance was initially similar before the start of EVNP, the “optimally perfused” kidneys (n = 5) became globally pink during perfusion and the remaining 2 “nonoptimally perfused” kidneys became pink but were also patchy.
FIGURE 3
FIGURE 3
Least square mean of hemodynamic, functional and electrolyte trends on ex vivo normothermic perfusion (EVNP). Overall, for the “optimally perfused” kidneys, red blood flow (RBF) (mL/min) gradually increased and stabilized after 120 minutes (A) whereas Renal Resistive Index (RRI) gradually decreased and stabilized after 120 minutes (B). Both RBF and RRI were variable during the first 60 minutes for the “nonoptimally perfused” kidneys but eventually improved and also stabilized after 120 minutes on EVNP. Urine output (mL/h) remained high in the “optimally perfused” kidneys (C). Perfusate lactate levels steadily increased with time in the nonoptimally perfused kidneys compared to relatively stable lactate levels in the perfusate of the optimally perfused group (D). Perfusate sodium levels steadily increased with time in the optimally perfused kidneys compared to relatively stable sodium levels in the perfusate of the nonoptimally perfused group (E). Oxygen consumption for both kidneys resulted in similar curves with a peak and eventual stable decrease (F). Creatinine clearance (G) and fractional excretion of sodium (H) were more favorable in the optimally perfused kidneys.
FIGURE 4
FIGURE 4
Histology of prebiopsy and postbiopsy. Hematoxylin and eosin, 20×, 2 μm. A, Optimally perfused preperfusion biopsy. B, Optimally perfused postperfusion biopsy. C, Nonoptimally perfused preperfusion biopsy. D, Nonoptimally perfused postperfusion biopsy. Arrows represent examples of oxalate crystals, arrow heads represent sloughed epithelial cells, and asterisk represent cytoplasmic blebbing.
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