Wijermars 2016 Kidney Int
| Wijermars LG, Schaapherder AF, de Vries DK, Verschuren L, Wuest RC, Kostidis S, Mayboroda OA, Prins F, Ringers J, Bierau J, Bakker JA, Kooistra T, Lindeman JH (2016) Defective postreperfusion metabolic recovery directly associates with incident delayed graft function. Kidney Int 90:181-91. |
Wijermars LG, Schaapherder AF, de Vries DK, Verschuren L, Wuest RC, Kostidis S, Mayboroda OA, Prins F, Ringers J, Bierau J, Bakker JA, Kooistra T, Lindeman Jan HN (2016) Kidney Int
Abstract: Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF. This report is based on sequential studies of 66 eligible patients of which 22 experienced DGF. Grafts with no DGF immediately recovered aerobic respiration as indicated by prompt cessation of lactate release following reperfusion. In contrast, grafts with DGF failed to recover aerobic respiration and showed persistent adenosine triphosphate catabolism indicated by a significant persistently low post reperfusion tissue glucose-lactate ratio and continued significant post-reperfusion lactate and hypoxanthine release (net arteriovenous difference for lactate and hypoxanthine at 30 minutes). The metabolic data for the group with DGF point to a persistent post reperfusion mitochondrial defect, confirmed by functional (respirometry) and morphological analyses. The archetypical mitochondrial stabilizing peptide SS-31 significantly preserved mitochondrial function in human kidney biopsies following simulated ischemia reperfusion. Thus, development of DGF is preceded by a profound post-reperfusion metabolic deficit resulting from severe mitochondrial damage. Strategies aimed at preventing DGF should be focused on safeguarding a minimally required post-reperfusion metabolic competence.
Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. • Keywords: Human, Injury, Ischemia, Kidney transplantation, Metabolism, Reperfusion
• O2k-Network Lab: NL Amsterdam Wuest RC, NL Maastricht Bierau J, NL Leiden Lindeman JHN
Labels: MiParea: Respiration, mt-Structure;fission;fusion, mt-Membrane, mt-Medicine, Patients, Pharmacology;toxicology
Stress:Ischemia-reperfusion Organism: Human Tissue;cell: Kidney Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase
Coupling state: OXPHOS Pathway: N, S, NS, ROX HRR: Oxygraph-2k
2016-07
