Pharmacological Protection of Kidney Grafts from Cold Perfusion-Induced Injury

Krzywonos‐Zawadzka, Anna; Franczak, Aleksandra; Möser, Michael; Olejnik, Agnieszka; Sawicki, Grzegorz; Bil‐Lula, Iwona

doi:10.1155/2019/9617087

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…Current novel treatment methods tested in animal models are centred around ameliorating HMP-induced injuries of kidney grafts [51]. A minimally invasive method called rapid sampling microdialysis (rsMD), which was developed in a porcine HMP model [52], may help monitor tissue ATP levels and other metabolic markers during MP in real-time, promoting further investigations into the relationship of MP temperature and renal tissue ATP.…”

Section: The Effects Of Higher Perfusion Temperatures (>4-10 • C) On mentioning

confidence: 99%

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Bellini

Yiu

Nozdrin

et al. 2019

JCM

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The recent advances in machine perfusion (MP) technology involve settings ranging between hypothermic, subnormothermic, and normothermic temperatures. Tissue level adenosine triphosphate (ATP) is a long-established marker of viability and functionality and is universal for all organs. In the midst of a growing number of complex clinical parameters for the quality assessment of graft prior to transplantation, a revisit of ATP may shed light on the underlying reconditioning mechanisms of different perfusion temperatures in the form of restoration of metabolic and energy status. This article aims to review and critically analyse animal and preclinical human studies (discarded grafts) during MP of three abdominal organs (liver, kidney, and pancreas) in which ATP was a primary endpoint. A selective review of recent novel reconditioning approaches relevant to mitigation of graft ischaemia-reperfusion injury via MP and for different perfusion temperatures was also conducted. With a current reiterated interest for oxygenation during MP, a re-introduction of tissue ATP levels may be valuable for graft viability assessment prior to transplantation. Further studies may help delineate the benefits of selective perfusion temperatures on organs viability.

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Section: The Effects Of Higher Perfusion Temperatures (>4-10 • C) On mentioning

confidence: 99%

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Bellini

Yiu

Nozdrin

et al. 2019

JCM

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“…Besides allowing the kidney to regain its function, NMP can be used to keep the kidney in a controlled state allowing close observation and viability assessment enabling successful transplantation of declined kidneys. From a renal aging perspective, machine perfusion provides the window of opportunity to add therapies to a functioning organ extracorporeally ( Krzywonos-Zawadzka et al, 2019 ; Hosgood et al, 2020 ) ( Figure 2 ). Together with gene-manipulating therapies, nanoparticles, anti-inflammatory agents, anti-thrombolytic agents, and monoclonal antibodies directed against complement activation ( Jager et al, 2017 ), senotherapeutic agents could represent an important strategy of intervention.…”

Section: Future Perspective In Senotherapy: Application In Transplantation Fieldmentioning

confidence: 99%

Targeting Premature Renal Aging: from Molecular Mechanisms of Cellular Senescence to Senolytic Trials

et al. 2021

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The biological process of renal aging is characterized by progressive structural and functional deterioration of the kidney leading to end-stage renal disease, requiring renal replacement therapy. Since the discovery of pivotal mechanisms of senescence such as cell cycle arrest, apoptosis inhibition, and the development of a senescence-associated secretory phenotype (SASP), efforts in the understanding of how senescent cells participate in renal physiological and pathological aging have grown exponentially. This has been encouraged by both preclinical studies in animal models with senescent cell clearance or genetic depletion as well as due to evidence coming from the clinical oncologic experience. This review considers the molecular mechanism and pathways that trigger premature renal aging from mitochondrial dysfunction, epigenetic modifications to autophagy, DNA damage repair (DDR), and the involvement of extracellular vesicles. We also discuss the different pharmaceutical approaches to selectively target senescent cells (namely, senolytics) or the development of systemic SASP (called senomorphics) in basic models of CKD and clinical trials. Finally, an overview will be provided on the potential opportunities for their use in renal transplantation during ex vivo machine perfusion to improve the quality of the graft.

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“…IRI is of superior relevance in transplant medicine, as it significantly affects both the available donor pool as well as the lifespan of transplanted organs. IRI affects the current donor pool since especially marginal organs are known to suffer severely from IRI, adding additional risk of graft failure [10][11][12]. In order to utilize more marginal organs from extended criteria donors, further improvements are necessary to ameliorate IRI.…”

Section: Introductionmentioning

confidence: 99%

HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation

Mohr

Brockmann

Becker

2020

IJMS

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To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

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Pharmacological Protection of Kidney Grafts from Cold Perfusion-Induced Injury

Cited by 8 publications

References 45 publications

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models

Targeting Premature Renal Aging: from Molecular Mechanisms of Cellular Senescence to Senolytic Trials

HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation

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