Impact of device variability and protocol differences on kidney function during normothermic machine perfusion: A comparative study using porcine and human kidneys.

Introduction: A growing interest in renal normothermic machine perfusion (NMP) has resulted in more clinically available perfusion devices. While all perfusion systems have the same aim, there are significant differences in their circuits, pumps, sensors, and software. Therefore, our objective was to assess the impact of different perfusion protocols and devices on kidney function and perfusion parameters during NMP.

Ex-Vivo Kidney Perfusion With Hemoglobin-Based Oxygen Carriers, Red Blood Cells, or No Oxygen Carrier.

Introduction: Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity to assess and improve organ viability prior to transplantation. This study explored the necessity of an oxygen carrier during NMP and whether the hemoglobin-based oxygen carrier (HBOC-201) is a suitable alternative to red blood cells (RBCs).

Methods: Porcine kidneys were perfused with a perfusion solution containing either no-oxygen carrier, RBCs, or HBOC-201 for 360 min at 37°C.

Culturing Conditions Dictate the Composition and Pathways Enrichment of Human and Rat Perirenal Adipose-Derived Stromal Cells' Secretomes.

Understanding the impact of various culturing strategies on the secretome composition of adipose-derived stromal cells (ASC) enhances their therapeutic potential. This study investigated changes in the secretome of perirenal ASC (prASC) under different conditions: normoxia, cytokine exposure, high glucose, hypoxia, and hypoxia with high glucose. Using mass spectrometry and enrichment clustering analysis, we found that normoxia enriched pathways related to extracellular matrix (ECM) organization, platelet degranulation, and insulin-like growth factor (IGF) transport and uptake.

Magnetic resonance imaging as a noninvasive adjunct to conventional assessment of functional differences between kidneys in vivo and during ex vivo normothermic machine perfusion.

Normothermic machine perfusion (NMP) is increasingly considered for pretransplant kidney quality assessment. However, fundamental questions about differences between in vivo and ex vivo renal function, as well as the impact of ischemic injury on ex vivo physiology, remain unanswered. This study utilized magnetic resonance imaging (MRI), alongside conventional parameters to explore differences between in vivo and ex vivo renal function and the impact of warm ischemia on a kidney's behavior ex vivo.

The association between hemoglobin levels and renal function parameters during normothermic machine perfusion: A retrospective cohort study using porcine kidneys.

Background: Ex vivo normothermic machine perfusion (NMP) is a promising tool for assessing an isolated kidney prior to transplantation. However, there is no consensus on the perfusate's optimal oxygen-carrying capacity to support renal function. To investigate the association of hemoglobin levels with renal function parameters, a retrospective analysis of isolated, normothermically, perfused porcine kidneys was performed.

Red blood cells as oxygen carrier during normothermic machine perfusion of kidney grafts: Friend or foe?

Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP.

Utilizing pathophysiological concepts of ischemia-reperfusion injury to design renoprotective strategies and therapeutic interventions for normothermic ex vivo kidney perfusion.

Normothermic machine perfusion (NMP) has emerged as a promising tool for the preservation, viability assessment, and repair of deceased-donor kidneys prior to transplantation. These kidneys inevitably experience a period of ischemia during donation, which leads to ischemia-reperfusion injury when NMP is subsequently commenced. Ischemia-reperfusion injury has a major impact on the renal vasculature, metabolism, oxygenation, electrolyte balance, and acid-base homeostasis.

Furosemide attenuates tubulointerstitial injury and allows functional testing of porcine kidneys during normothermic machine perfusion.

Background: Normothermic machine perfusion (NMP) is a promising pretransplant kidney quality assessment platform, but it remains crucial to increase its diagnostic potential while ensuring minimal additional injury to the already damaged kidney. Interventions that alter tubular transport can influence renal function and injury during perfusion. This study aimed to determine whether furosemide and desmopressin affect renal function and injury during NMP.

Effects of kidney perfusion on renal stiffness and tissue fluidity measured with tomoelastography in an MRI-compatible model.

Stiffness plays a vital role in diagnosing renal fibrosis. However, perfusion influences renal stiffness in various chronic kidney diseases. Therefore, we aimed to characterize the effect of tissue perfusion on renal stiffness and tissue fluidity measured by tomoelastography based on multifrequency magnetic resonance elastography in an model.

Considerable Variability Among Transplant Nephrologists in Judging Deceased Donor Kidney Offers.

Introduction: Transplant clinicians may disagree on whether or not to accept a deceased donor kidney offer. We investigated the interobserver variability between transplant nephrologists regarding organ acceptance and whether the use of a prediction model impacted their decisions.

Methods: We developed an observational online survey with 6 real-life cases of deceased donor kidneys offered to a waitlisted recipient.

The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors.

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney.

Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available.

Expanding the Horizons of Pre-Transplant Renal Vascular Assessment Using Ex Vivo Perfusion.

Recently, immense efforts have focused on improving the preservation of (sub)optimal donor organs by means of ex vivo perfusion, which enables the opportunity for organ reconditioning and viability assessment. However, there is still no biomarker that correlates with renal viability. Therefore, it is essential to explore new techniques for pre-transplant assessment of organ quality to guarantee successful long-term transplantation outcomes.

Pathophysiological Changes in the Hemostatic System and Antithrombotic Management in Kidney Transplant Recipients.

Nowadays, the main cause for early graft loss is renal graft thrombosis because kidney transplant outcomes have improved drastically owing to advances in immunological techniques and immunosuppression. However, data regarding the efficacy of antithrombotic therapy in the prevention of renal graft thrombosis are scarce. Adequate antithrombotic management requires a good understanding of the pathophysiological changes in the hemostatic system in patients with end-stage kidney disease (ESKD).

Prolonged Controlled Oxygenated Rewarming Improves Immediate Tubular Function and Energetic Recovery of Porcine Kidneys During Normothermic Machine Perfusion.

Background: Normothermic machine perfusion (NMP) is typically performed after a period of hypothermic preservation, which exposes the kidney to an abrupt increase in temperature and intravascular pressure. The resultant rewarming injury could be alleviated by gradual rewarming using controlled oxygenated rewarming (COR). This study aimed to establish which rewarming rate during COR results in the best protective effect on renal rewarming injury during subsequent NMP.

Kidney utilization in the Netherlands - do we optimally use our donor organs?

Background: To ensure optimal utilization of deceased donor kidneys, it is important to understand the precise reasons why kidneys are discarded. In this study we aimed to obtain a comprehensive overview of kidney utilization and discard during the entire donation process in the Netherlands.

Methods: In this retrospective cohort study we analysed kidney utilization of 3856 kidneys in the Netherlands between 1 January 2015 and 31 December 2020.

Magnetic resonance imaging during warm ex vivo kidney perfusion.

Background: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable.

Normothermic machine perfusion of kidneys: current strategies and future perspectives.

Purpose Of Review: This review aims to summarize the latest original preclinical and clinical articles in the setting of normothermic machine perfusion (NMP) of kidney grafts.

Recent Findings: Kidney NMP can be safely translated into the clinical routine and there is increasing evidence that NMP may be beneficial in graft preservation especially in marginal kidney grafts. Due to the near-physiological state during NMP, this technology may be used as an ex-vivo organ assessment and treatment platform.

A Novel Aminomethacrylate-Based Copolymer for Solubility Enhancement-From Radical Polymer Synthesis to Manufacture and Characterization of Amorphous Solid Dispersions.

The present study covers the synthesis, purification and evaluation of a novel aminomethacrylate-based copolymer in terms of its suitability for improving the solubility and in vitro release of poorly water-soluble drug compounds. The new copolymer was synthesized by solvent polymerization with radical initiation and by use of a chain transfer agent. Based on its composition, it can be considered as a modified type of dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate "EUDRAGIT E PO" (ModE).

Development of Gold Nanoparticle-Based SERS Substrates on TiO-Coating to Reduce the Coffee Ring Effect.

Hydrophilic surface-enhanced Raman spectroscopy (SERS) substrates were prepared by a combination of TiO-coatings of aluminium plates through a direct titanium tetraisopropoxide (TTIP) coating and drop coated by synthesised gold nanoparticles (AuNPs). Differences between the wettability of the untreated substrates, the slowly dried Ti(OH) substrates and calcinated as well as plasma treated TiO substrates were analysed by water contact angle (WCA) measurements. The hydrophilic behaviour of the developed substrates helped to improve the distribution of the AuNPs, which reflects in overall higher lateral SERS enhancement.

Prolonged Organ Extraction Time Negatively Impacts Kidney Transplantation Outcome.

Following cold aortic flush in a deceased organ donation procedure, kidneys never reach the intended 0-4°C and stay ischemic at around 20°C in the donor's body until actual surgical retrieval. Therefore, organ extraction time could have a detrimental influence on kidney transplant outcome. We analyzed the association between extraction time and kidney transplant outcome in multicenter data of 5,426 transplant procedures from the Dutch Organ Transplantation Registry (NOTR) and 15,849 transplant procedures from the United Network for Organ Sharing (UNOS).

Antithrombotic Management in Adult Kidney Transplantation: A European Survey Study.

In kidney transplantation (KTx), renal graft thrombosis (RGT) is one of the main reasons for early graft loss. Although evidence-based guidance on prevention of RGT is lacking, thromboprophylaxis is widely used. The aim of this survey was to obtain a European view of the different thromboprophylactic strategies applied in KTx.

Magnetic resonance imaging assessment of renal flow distribution patterns during ex vivo normothermic machine perfusion in porcine and human kidneys.

Acceptance criteria of deceased donor organs have gradually been extended toward suboptimal quality, posing an urgent need for more objective pre-transplant organ assessment. Ex vivo normothermic machine perfusion (NMP) combined with magnetic resonance imaging (MRI) could assist clinicians in deciding whether a donor kidney is suitable for transplantation. Aim of this study was to characterize the regional distribution of perfusate flow during NMP, to better understand how ex vivo kidney assessment protocols should eventually be designed.

Prolonged ex-vivo normothermic kidney perfusion: The impact of perfusate composition.

Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters.

Renal Normothermic Machine Perfusion: The Road Toward Clinical Implementation of a Promising Pretransplant Organ Assessment Tool.

The increased utilization of high-risk renal grafts for transplantation requires optimization of pretransplant organ assessment strategies. Current decision-making methods to accept an organ for transplantation lack overall predictive power and always contain an element of subjectivity. Normothermic machine perfusion (NMP) creates near-physiological conditions, which might facilitate a more objective assessment of organ quality before transplantation.