The effect of Hemarina on renal injury in a warming-up AQIX perfused rat kidney model

Deckers, E.A. (Eric Arnoud) (2014) The effect of Hemarina on renal injury in a warming-up AQIX perfused rat kidney model. thesis, Medicine.

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Abstract

Background: During organ transplantation, organs that have been statically cold stored are inevitably exposed to reperfusion injury. Hypothermic- followed by normothermic machine perfusion prior to transplantation is known to be beneficial in terms of preservation of the organ, after a period of cold storage. Compared to the sudden onset of a higher temperature, gradual warming-up represents a strategy to ameliorate organ quality. In this study we hypothesized that perfusion at increasing temperatures urges the use of an oxygen carrier, as metabolism rises with rising temperatures. We therefore evaluated the use of an oxygen carrier, Hemarina M-101, in an isolated kidney perfusion circuit. As a result, a different perfusion solution (AQIX) to maintain acid-base balance in a warming-up setting was also evaluated. Materials and Methods: Male Lewis rats left kidneys were statically cold stored in University of Wisconsin preservation solution for 24 hours at 4°C. After cold storage kidneys were connected to an isolated perfused kidney device and perfused with oxygenated AQIX enriched with albumin and creatinin. Two groups (n=7), with or without Hemarina M-101, were formed. Hypothermic perfusion for 30 minutes at 10°C was followed by gradually warming-up to 37°C. This normothermic part of the perfusion lasted for another 60 minutes. Perfusion dynamics, renal function and injury biomarkers were assessed during the 90 minutes perfusion period. Mitochondrial function and endothelial damage markers were measured at the end of perfusion. Results: Perfusion dynamics, (potential) injury biomarkers and functional markers were observed in the AQIX with M101 vs AQIX without M101. Perfusion dynamics such as flow, resistance and oxygen consumption showed a significant difference at the expense of the M101 group from 50 minutes on, till the end of perfusion (p≤0.05). Injury markers such as LDH, ASAT, LPO and creatinin did not show significant differences between groups. Total urine production and GFR as functional parameters and mitochondrial function of the organ showed no differences between groups. PCR measurements regarding HSP70, Caspase-3, KIM-1, BCL2, BAX, BAX/BCL2, ICAM, VCAM en p-selectin were not different. Immunohistochemistry for ICAM upreglulation did not show any differences between groups. Conclusion: In conclusion, the addition of Hemarina in combination with AQIX in a warming-up setting is not beneficial as there are no conclusive differences between the groups. AQIX however demonstrated to be a stable preservation solution based on little fluctuations in pH over perfusion time.

Item Type:	Thesis (Thesis)
Supervisor name:	Mahboub, P. PhD and Leuvenink, prof. dr. H.G.D.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:06
Last Modified:	25 Jun 2020 11:06
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2583

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