Renal biopsies from donors with acute kidney injury show different molecular patterns according to the post-transplant function.

The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty kidney biopsies from donors with (20) and without AKI (20) were selected and then subdivided according to the post-transplant outcome defined as a threshold of 45 ml/min for the eGFR at 1 year from transplantation. Tissue homogenates were analysed by western blot to assess how the levels of 17 pre-selected proteins varied across the four groups. Samples from AKI kidneys with a poor outcome showed a fourfold increase in the levels of PPARg and twofold reduction of STAT1 compared to the other groups (p < 0.05). On the contrary, antioxidant enzymes including TRX1 and PRX3 were increased in the AKI kidneys with a good outcome (p < 0.05). An opposite trend was observed for the detoxifying enzyme GSTp which was significantly increased in the AKI group with poor versus good outcome (p < 0.05). The importance of lipid metabolism (PPARg) and inflammatory signals (STAT1) in the function recovery of these kidneys hints to the therapeutical targeting of the involved pathways in the setting of organ reconditioning.

sp3 -Rich Heterocycle Synthesis on DNA: Application to DNA-Encoded Library Production.

DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp2 -rich molecules. Herein, we show that sp3 -rich mono- and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space.

Impaired O2 unloading from stored blood results in diffusion-limited O2 release at tissues: evidence from human kidneys.

ABSTRACT: The volume of oxygen drawn from systemic capillaries down a partial pressure gradient is determined by the oxygen content of red blood cells (RBCs) and their oxygen-unloading kinetics, although the latter is assumed to be rapid and, therefore, not a meaningful factor. Under this paradigm, oxygen transfer to tissues is perfusion-limited. Consequently, clinical treatments to optimize oxygen delivery aim at improving blood flow and arterial oxygen content, rather than RBC oxygen handling. Although the oxygen-carrying capacity of blood is increased with transfusion, studies have shown that stored blood undergoes kinetic attrition of oxygen release, which may compromise overall oxygen delivery to tissues by causing transport to become diffusion-limited. We sought evidence for diffusion-limited oxygen release in viable human kidneys, normothermically perfused with stored blood. In a cohort of kidneys that went on to be transplanted, renal respiration correlated inversely with the time-constant of oxygen unloading from RBCs used for perfusion. Furthermore, the renal respiratory rate did not correlate with arterial O2 delivery unless this factored the rate of oxygen-release from RBCs, as expected from diffusion-limited transport. To test for a rescue effect, perfusion of kidneys deemed unsuitable for transplantation was alternated between stored and rejuvenated RBCs of the same donation. This experiment controlled oxygen-unloading, without intervening ischemia, holding all non-RBC parameters constant. Rejuvenated oxygen-unloading kinetics improved the kidney's oxygen diffusion capacity and increased cortical oxygen partial pressure by 60%. Thus, oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood, which has implications in scenarios, such as ex vivo organ perfusion, major hemorrhage, and pediatric transfusion. This trial was registered at www.clinicaltrials.gov as #ISRCTN13292277.

Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals.

Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.

Ethical Principles Do Not Support Mandatory Preanesthesia Pregnancy Screening Tests: A Narrative Review.

Respect for patient autonomy is a pillar of medical ethics, manifested predominantly through informed consent. Mandatory (routine) nonconsented preoperative urine pregnancy testing does not adequately respect patient autonomy, is potentially coercive, and has the potential to cause harm medically, psychologically, socially, and financially. Inaccuracies in pregnancy testing can result in false-positive and false-negative results, especially in early pregnancy. There is substantial scientific evidence that anesthesia is not harmful to the fetus, raising the question of whether pregnancy testing provides substantial benefit to the patient. Not performing a preanesthesia pregnancy test has not been associated with significant medicolegal consequences. We review the ethical implications of mandatory preanesthesia pregnancy testing in light of these facts.

Dolutegravir-associated resistance mutations after first-line treatment failure in Brazil.

BACKGROUND: Since January 2017, the recommended first-line antiretroviral regimen in Brazil is the fixed-dose combination of tenofovir plus lamivudine with dolutegravir (TL + D). According to the literature, integrase resistance-associated mutations (INRAMs) are rarely found upon virologic failure to first-line dolutegravir plus two nucleoside reverse transcriptase inhibitors. We evaluated the HIV antiretroviral genotypic resistance profile of patients referred for genotyping in the public health system who failed first-line TL + D after at least six months of therapy on or before December 31, 2018. METHODS: HIV Sanger sequences of the pol gene were generated from plasma of patients with confirmed virologic failure to first-line TL + D in the Brazilian public health system before December 31, 2018. RESULTS: One hundred thirteen individuals were included in the analysis. Major INRAMs were detected in seven patients (6.19%), four with R263K, one with G118R, one with E138A, and one with G140R. Four patients with major INRAMs also had the K70E and M184V mutations in the RT gene. Sixteen (14.2%) additional individuals presented minor INRAMs, and five (4,42%) patients had both major and minor INRAMS. Thirteen (11.5%) patients also presented mutations in the RT gene selected by tenofovir and lamivudine, including four with both the K70E and M184V mutations and four with only M184V. The integrase mutations L101I and T124A, which are in the in vitro pathway for integrase inhibitor resistance, were found in 48 and 19 patients, respectively. Mutations not related to TL + D, thus probable transmitted resistance mutations (TDR), were present in 28 patients (24.8%): 25 (22.1%) to nucleoside reverse transcriptase inhibitors, 19 (16.8%) to non-nucleoside reverse transcriptase inhibitors, and 6 (5.31%) to protease inhibitors. CONCLUSIONS: In marked contrast to previous reports, we report a relatively high frequency of INRAMs among selected patients failing first-line TL + D in the public health system in Brazil. Possible reasons for this discrepancy include delays in detecting virologic failure, patients inadvertently on dolutegravir monotherapy, TDR, and/or infecting subtype.

Connecting Gut Microbial Diversity with Plasma Metabolome and Fecal Bile Acid Changes Induced by the Antibiotics Tobramycin and Colistin Sulfate.

The diversity of microbial species in the gut has a strong influence on health and development of the host. Further, there are indications that the variation in expression of gut bacterial metabolic enzymes is less diverse than the taxonomic profile, underlying the importance of microbiome functionality, particularly from a toxicological perspective. To address these relationships, the gut bacterial composition of Wistar rats was altered by a 28 day oral treatment with the antibiotics tobramycin or colistin sulfate. On the basis of 16S marker gene sequencing data, tobramycin was found to cause a strong reduction in the diversity and relative abundance of the microbiome, whereas colistin sulfate had only a marginal impact. Associated plasma and fecal metabolomes were characterized by targeted mass spectrometry-based profiling. The fecal metabolome of tobramycin-treated animals had a high number of significant alterations in metabolite levels compared to controls, particularly in amino acids, lipids, bile acids (BAs), carbohydrates, and energy metabolites. The accumulation of primary BAs and significant reduction of secondary BAs in the feces indicated that the microbial alterations induced by tobramycin inhibit bacterial deconjugation reactions. The plasma metabolome showed less, but still many alterations in the same metabolite groups, including reductions in indole derivatives and hippuric acid, and furthermore, despite marginal effects of colistin sulfate treatment, there were nonetheless systemic alterations also in BAs. Aside from these treatment-based differences, we also uncovered interindividual differences particularly centering on the loss of Verrucomicrobiaceae in the microbiome, but with no apparent associated metabolite alterations. Finally, by comparing the data set from this study with metabolome alterations in the MetaMapTox database, key metabolite alterations were identified as plasma biomarkers indicative of altered gut microbiomes resulting from a wide activity spectrum of antibiotics.

Cardiorespiratory Optimisation By Arteriovenous fistula Ligation after renal Transplantation (COBALT): study protocol for a multicentre randomised interventional feasibility trial.

INTRODUCTION: Cardiovascular events are a major cause of mortality following successful kidney transplantation.Arteriovenous fistulas (AVFs) are considered the best option for haemodialysis, but may contribute to this excess mortality because they promote adverse cardiac remodelling and ventricular hypertrophy. This raises the question whether recipients with a well-functioning kidney transplant should undergo elective AVF ligation. METHODS AND ANALYSIS: The COBALT feasibility study is a multicentre interventional randomised controlled trial (RCT) that will randomise renal transplant patients with stable graft function and a working AVF on a 1:1 basis to standard care (continued conservative management) or to AVF ligation. All patients will perform cardiopulmonary exercise testing (CPET) on recruitment and 6 months later. Daily functioning and quality of life will be additionally assessed by questionnaire completion and objective measure of physical activity. The primary outcome-the proportion of approached patients who complete the study (incorporating rates of consent, receipt of allocated intervention and completion of both CPETs without withdrawal)-will determine progression to a full-scale RCT. Design of the proposed RCT will be informed by an embedded qualitative assessment of participant and healthcare professional involvement. ETHICS AND DISSEMINATION: This study has been approved by the East Midlands-Derby Research Ethics Committee (22/EM/0002) and the Health Research Authority. The results of this work will be disseminated academically through presentation at national and international renal meetings and via open access, peer-reviewed outputs. Existing networks of renal patient groups will also be used to disseminate the study findings to other key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN49033491.

Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment.

An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.

How does computed tomography inform our understanding of shoulder kinematics? A structured review.

The objective of this structured review was to review how computed tomography (CT) scanning has been used to measure the kinematics of the shoulder. A literature search was conducted using Evidence-based Medicine Reviews (Embase) and PubMed. In total, 29 articles were included in the data extraction process. Forty percent of the studies evaluated healthy participants' shoulder kinematics. The glenohumeral joint was the most studied, followed by the scapulothoracic, acromioclavicular, and sternoclavicular joints. Three-dimensional computed tomography (3DCT) and 3DCT with biplane fluoroscopy are the two primary imaging techniques that have been used to measure shoulder joints' motion under different conditions. Finally, many discrepancies in the reporting of the examined motions were found. Different authors used different perspectives and planes to report similar motions, which results in confusion and misunderstanding of the actual examined motion. The use of 3DCT has been widely used in the examination of shoulder kinematics in a variety of populations with varying methods employed. Future work is needed to extend these methodologies to include more diverse populations, to examine the shoulder complex as a whole, and to standardize their reporting of motion examined to make study to study comparisons possible.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients.

BACKGROUND: Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. OBJECTIVE: To examine the cognitive function of adults with and without EDS and with and without ApoEε4. METHODS: A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. RESULTS: Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. CONCLUSIONS: Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

ANTECEDENTES: Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. OBJETIVO: Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. MéTODOS: Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. RESULTADOS: A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. CONCLUSõES: A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients / Interação entre genótipos da apolipoproteína E, sonolência excessiva diurna e função cognitiva em pacientes com apneia obstrutiva do sono

Abstract Background Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. Objective To examine the cognitive function of adults with and without EDS and with and without ApoEε4. Methods A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. Results Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. Conclusions Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

Resumo Antecedentes Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. Objetivo Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. Métodos Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. Resultados A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. Conclusões A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Environmental Changes and the Impact on the Human Infections by Dengue, Chikungunya and Zika Viruses in Northern Brazil, 2010-2019.

Environmental changes are among the main factors that contribute to the emergence or re-emergence of viruses of public health importance. Here, we show the impact of environmental modifications on cases of infections by the dengue, chikungunya and Zika viruses in humans in the state of Tocantins, Brazil, between the years 2010 and 2019. We conducted a descriptive and principal component analysis (PCA) to explore the main trends in environmental modifications and in the cases of human infections caused by these arboviruses in Tocantins. Our analysis demonstrated that the occurrence of El Niño, deforestation in the Cerrado and maximum temperatures had correlations with the cases of infections by the Zika virus between 2014 and 2016. El Niño, followed by La Niña, a gradual increase in precipitation and the maximum temperature observed between 2015 and 2017 were shown to have contributed to the infections by the chikungunya virus. La Niña and precipitation were associated with infections by the dengue virus between 2010 and 2012 and El Niño contributed to the 2019 outbreak observed within the state. By PCA, deforestation, temperatures and El Niño were the most important variables related to cases of dengue in humans. We conclude from this analysis that environmental changes (deforestation and climate change) presented a strong influence on the human infections caused by the dengue, chikungunya and Zika viruses in Tocantins from 2010 to 2019.

Bioreactor media for treatment of slag leachate.

Blast furnace slag (BFS) used in the road construction as base/subbase materials leads to leachate problems under poor drainage conditions. The BSF leachate is a source of high pH, sulfur, and dissolved solids which will be affected to surrounding ecosystem. A column experiment was performed to evaluate the treatment of BFS leachate by media commonly used in passive treatment systems. The treatment efficiency of column media was assessed for inorganic (gravel and limestone) and organic (peat and mushroom compost) with zero-valent iron (ZVI). Columns were dosed with experimentally generated BFS leachate and operated under residence times of 7 and 14 days. The column depths of 45 cm and 75 cm allowed for determination of the role of anoxic conditions in the transformation, precipitation, and adsorption of dissolved constituents. The organic treatments were more effective for reducing pH, TDS, sulfate, and total sulfur. Mushroom compost, with ZVI and a residence time of 14 days, was the most effective matrix for the removal of sulfate (67%), and total sulfur (72%). Peat treatments resulted in the lowest pH at 6.34; however, concentrations of Al, Fe, Mg, and Mn were elevated. Organic biofilters utilizing sulfate-reducing bacteria (SRB) and ZVI may prove to be useful for treating BFS leachate and other sources of sulfur and TDS pollution.

Re-emergence of mayaro virus and coinfection with chikungunya during an outbreak in the state of Tocantins/Brazil.

OBJECTIVE: To perform a molecular screening to detect infections by the mayaro virus and possible coinfections with Chikungunya during an outbreak in the state of Tocantins/Brazil in 2017. RESULTS: Of a total 102 samples analyzed in this study, 6 cases were identified with simultaneous infection between mayaro and chikungunya viruses (5.88%). In these 6 samples, the mean Cycle threshold (Ct) for CHIKV was 26.87 (SD ± 10.54) and for MAYV was 29.58 (SD ± 6.34). The mayaro sequences generated showed 95-100% identity to other Brazilian sequences of this virus and with other MAYV isolates obtained from human and arthropods in different regions of the world. The remaining samples were detected with CHIKV monoinfection (41 cases), DENV monoinfection (50 cases) and coinfection between CHIKV/DENV (5 cases). We did not detect MAYV monoinfections.

Build-Couple-Transform: A Paradigm for Lead-like Library Synthesis with Scaffold Diversity.

High-throughput screening provides one of the most common ways of finding hit compounds. Lead-like libraries, in particular, provide hits with compatible functional groups and vectors for structural elaboration and physical properties suitable for optimization. Library synthesis approaches can lead to a lack of chemical diversity because they employ parallel derivatization of common building blocks using single reaction types. We address this problem through a "build-couple-transform" paradigm for the generation of lead-like libraries with scaffold diversity. Nineteen transformations of a 4-oxo-2-butenamide scaffold template were optimized, including 1,4-cyclizations, 3,4-cyclizations, reductions, and 1,4-additions. A pool-transformation approach efficiently explored the scope of these transformations for nine different building blocks and synthesized a >170-member library with enhanced chemical space coverage and favorable drug-like properties. Screening revealed hits against CDK2. This work establishes the build-couple-transform concept for the synthesis of lead-like libraries and provides a differentiated approach to libraries with significantly enhanced scaffold diversity.

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. There are reports on the application of mesenchymal stromal/stem cells, multipotent adult progenitor cells and microRNA during kidney NMP, with first data indicating that these therapies indeed lead to a decrease in inflammatory response and kidney injury. Together with the demonstrated possibility of prolonged ex-vivo perfusion without significant graft damage, NMP could not only be used as a tool to perform preimplant graft assessment. Some evidence exists that it truly has the potential to be a platform to treat and repair injured kidney grafts, thereby significantly reducing the number of declined organs. SUMMARY: Kidney NMP is feasible and can potentially increase the donor pool not only by preimplant graft assessment, but also by ex-vivo graft treatment.