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Int J Mol Sci. 2019 Apr 23;20(8). pii: E1992. doi: 10.3390/ijms20081992.

Individual and Combined Impact of Oxygen and Oxygen Transporter Supplementation during Kidney Machine Preservation in a Porcine Preclinical Kidney Transplantation Model.

Kasil A1,2,3, Giraud S4,5, Couturier P6,7,8, Amiri A9,10, Danion J11,12, Donatini G13,14, Matillon X15,16,17,18, Hauet T19,20,21,22,23, Badet L24,25,26.

Author information

1
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. akasil2011@gmail.com.
2
Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers F-86000, France. akasil2011@gmail.com.
3
Service d'Urologie et de Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon F-69003, France. akasil2011@gmail.com.
4
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. giraudseb@yahoo.fr.
5
Service de Biochimie, CHU Poitiers, Poitiers F-86000, France. giraudseb@yahoo.fr.
6
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. pierre.couturier@outlook.fr.
7
Service de Biochimie, CHU Poitiers, Poitiers F-86000, France. pierre.couturier@outlook.fr.
8
Plate-forme Infrastrutures en Biologie Sante et Agronomie (IBiSA) MOdélisation Préclinique - Innovations Chirurgicale et Technologique (MOPICT), Domaine Expérimental du Magneraud, Surgères F-17700, France. pierre.couturier@outlook.fr.
9
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. akbar_amiri@hotmail.com.
10
Service d'Urologie et de Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon F-69003, France. akbar_amiri@hotmail.com.
11
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. jerome.danion@me.com.
12
Service de Chirurgie viscérale, CHU de Poitiers, Poitiers F-86000, France. jerome.danion@me.com.
13
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. gianluca.donatini@chu-poitiers.fr.
14
Service de Chirurgie viscérale, CHU de Poitiers, Poitiers F-86000, France. gianluca.donatini@chu-poitiers.fr.
15
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. xav.matillon@gmail.com.
16
Service d'Urologie et de Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon F-69003, France. xav.matillon@gmail.com.
17
Université Claude Bernard Lyon 1, Lyon F-69003, France. xav.matillon@gmail.com.
18
CarMeN Laboratory, INSERM U1060, Villeurbanne F-69100, France. xav.matillon@gmail.com.
19
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. thierry.hauet@gmail.com.
20
Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers F-86000, France. thierry.hauet@gmail.com.
21
Service de Biochimie, CHU Poitiers, Poitiers F-86000, France. thierry.hauet@gmail.com.
22
Plate-forme Infrastrutures en Biologie Sante et Agronomie (IBiSA) MOdélisation Préclinique - Innovations Chirurgicale et Technologique (MOPICT), Domaine Expérimental du Magneraud, Surgères F-17700, France. thierry.hauet@gmail.com.
23
FHU SUPORT 'SUrvival oPtimization in ORgan Transplantation', Poitiers F-86000, France. thierry.hauet@gmail.com.
24
INSERM U1082 (IRTOMIT), Poitiers F-86000, France. lionel.badet@chu-lyon.fr.
25
Service d'Urologie et de Chirurgie de la Transplantation, Hôpital Edouard Herriot, Lyon F-69003, France. lionel.badet@chu-lyon.fr.
26
Université Claude Bernard Lyon 1, Lyon F-69003, France. lionel.badet@chu-lyon.fr.

Abstract

Marginal kidney graft preservation in machine perfusion (MP) is well-established. However, this method requires improvement in order to mitigate oxidative stress during ischemia-reperfusion, by using oxygenation or an O2 carrier with anti-oxidant capacities (hemoglobin of the marine worm; M101). In our preclinical porcine (pig related) model, kidneys were submitted to 1h-warm ischemia, followed by 23 h hypothermic preservation in Waves® MP before auto-transplantation. Four groups were studied: W (MP without 100%-O2), W-O2 (MP with 100%-O2; also called hyperoxia), W-M101 (MP without 100%-O2 + M101 2 g/L), W-O2 + M101 (MP with 100%-O2 + M101 2 g/L) (n = 6/group). Results: Kidneys preserved in the W-M101 group showed lower resistance, compared to our W group. During the first week post-transplantation, W-O2 and W-M101 groups showed a lower blood creatinine and better glomerular filtration rate. KIM-1 and IL-18 blood levels were lower in the W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, fractional excretion of sodium and the proteinuria/creatinuria ratio remained higher in the W group, creatininemia was lower in the W-M101 group, and kidney fibrosis was lower in M101 groups. We concluded that supplementation with M101 associated with or without 100% O2 improved the Waves® MP effect upon kidney recovery and late graft outcome.

KEYWORDS:

dynamic/machine perfusion; hemoglobin; ischemia; kidney transplantation; oxygen

PMID:
31018558
PMCID:
PMC6514898
DOI:
10.3390/ijms20081992
[Indexed for MEDLINE]
Free PMC Article

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