The Role of Metabolomics in Current Concepts of Organ Preservation

Kvietkauskas, Mindaugas; Zitkute, Viktorija; Leber, Bettina; Strupas, Kęstutis; Stiegler, Philipp; Schemmer, Peter

doi:10.3390/ijms21186607

Cited by 19 publications

(13 citation statements)

References 67 publications

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“…Advances in IRI studies regarding its molecular mechanisms have led to different strategies that are used to reduce the detrimental effects of IRI. One of the modifiers of the ischemic phase is the use of machine perfusion (MP), which is a well-established approach for decreasing the incidence of DGF and improving late outcomes, especially for DCD and ECD [ 10 , 11 ]. MP offers the advantage of preventing mitochondrial and tissue damage.…”

Section: Introductionmentioning

confidence: 99%

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

et al. 2021

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Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and ET-3), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) during the reperfusion of human kidneys grafted from brain dead donors and later transplanted. The study group (n = 44) was analyzed according to the method of kidney storage: Group 1 underwent hypothermic machine perfusion (HMP) in the LifePort perfusion pump (n = 22), and Group 2 underwent static cold storage (SCS) (n = 22). The analysis of kidney function was performed daily during the first seven days after transplantation. The kidneys in Group 1 were characterized by higher absolute concentrations of ET-1, IL-18, and NGAL, as well as a lower concentration of ET-2 (p = 0.017) and ET-3. The relative increase of ET-1 (p = 0.033), ET-2, and ET-3 during reperfusion was lower in this group, while the relative decrease of NGAL was higher. Group 1 was also characterized by significant decrease of IL-18 (p = 0.026) and a tendency for better kidney function based on the higher total diuresis, higher glomerular filtration rate (GFR), higher potassium level, lower serum creatinine, and lower urea concentration during the seven-day postoperative observation period. The long-term beneficial impact of hypothermic machine perfusion on the outcome of transplanted kidneys may rely on the early modified proceedings and intensity of ischemia-reperfusion injury reflected by the dynamics of the concentrations of examined biomarkers.

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Section: Introductionmentioning

confidence: 99%

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

et al. 2021

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“…Furthermore, machine perfusion driven viability assessment during HMP/HOPE or NMP may support clinical decision in the acceptance or rejection of marginal liver allografts [ 4 , 6 , 184 ]. Besides refinement of the preservation techniques, the impact of hepatic dysfunction on macro- and micro-rheological parameters still need to be investigated, including metabolomics studies, to reveal better the local and systemic effects [ 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 ]. However, it would be interesting to overview it in a separate paper.…”

Section: Future Perspectives and Remaining Challengesmentioning

confidence: 99%

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

Németh

Pető

Magyar

et al. 2021

IJMS

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Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

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“…The ROS released by activated macrophages further amplify renal damage, activate complement system that sustained injury response. During reperfusion, platelets led to thrombus formation, reducing flow rate and mediating also vasoconstriction and inflammatory processes ( 4 , 14 , 168 , 172 ).…”

Section: Strategies Of Interventionmentioning

confidence: 99%

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

et al. 2021

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Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on development of innovative and dynamic preservation techniques, in order to assess graft function and promote regeneration by pharmacological intervention before transplantation. This review provides an overview of the current knowledge of these new preservation strategies by machine perfusions and pharmacological interventions at different timing possibilities: in the organ donor, ex-vivo during perfusion machine reconditioning or after implementation in the recipient. We will report therapies as anti-oxidant and anti-inflammatory agents, senolytics agents, complement inhibitors, HDL, siRNA and H2S supplementation. Renal delivery of pharmacologic agents during preservation state provides a window of opportunity to treat the organ in an isolated manner and a crucial route of administration. Even if few studies have been reported of transplantation after ex-vivo drugs administration, targeting the biological pathway associated to kidney failure (i.e. oxidative stress, complement system, fibrosis) might be a promising therapeutic strategy to improve the quality of various donor organs and expand organ availability.

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The Role of Metabolomics in Current Concepts of Organ Preservation

Cited by 19 publications

References 67 publications

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

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