Continuous Renal Replacement Therapy During Long-term Normothermic Machine Perfusion of Human Donor Livers for up to 7 D

Bianca Lascaris; Roland F Hoffmann; Maarten W N Nijsten; Robert J Porte; Vincent E de Meijer

doi:10.1097/TXD.0000000000001568

Continuous Renal Replacement Therapy During Long-term Normothermic Machine Perfusion of Human Donor Livers for up to 7 D

Transplant Direct. 2024 Jan 24;10(2):e1568. doi: 10.1097/TXD.0000000000001568. eCollection 2024 Feb.

Authors

Bianca Lascaris^{1

2}, Roland F Hoffmann³, Maarten W N Nijsten⁴, Robert J Porte^{1

5}, Vincent E de Meijer^{1

2}

Affiliations

¹ Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
² UMCG Comprehensive Transplant Center, Groningen, The Netherlands.
³ Department of Cardiothoracic Surgery, Section Extracorporeal Circulation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Critical Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ Division of HPB and Transplant Surgery, Department of Surgery, Erasmus MC Transplant Institute, Rotterdam, The Netherlands.

Abstract

Background: Normothermic machine perfusion (NMP) is used to preserve and test donor livers before transplantation. During NMP, the liver is metabolically active and produces waste products, which are released into the perfusate. In this study, we describe our simplified and inexpensive setup that integrates continuous renal replacement therapy (CRRT) with NMP for up to 7 d. We also investigated if the ultrafiltrate could be used for monitoring perfusate concentrations of small molecules such as glucose and lactate.

Methods: Perfusate composition (urea, osmolarity, sodium, potassium, chloride, calcium, magnesium, phosphate, glucose, and lactate) was analyzed from 56 human NMP procedures without CRRT. Next, in 6 discarded human donor livers, CRRT was performed during NMP by integrating a small dialysis filter (0.2 m²) into the circuit to achieve continuous ultrafiltration combined with continuous fluid substitution for up to 7 d.

Results: Within a few hours of NMP without CRRT, a linear increase in osmolarity and concentrations of urea and phosphate to supraphysiological levels was observed. After integration of CRRT into the NMP circuit, the composition of the perfusate was corrected to physiological values within 12 h, and this homeostasis was maintained during NMP for up to 7 d. Glucose and lactate levels, as measured in the CRRT ultrafiltrate, were strongly correlated with perfusate levels (r = 0.997, P < 0.001 and r = 0.999, P < 0.001, respectively).

Conclusions: The integration of CRRT into the NMP system corrected the composition of the perfusate to near-physiological values, which could be maintained for up to 7 d. The ultrafiltrate can serve as an alternative to the perfusate to monitor concentrations of small molecules without potentially compromising sterility.