The objective of the study is to analyze the factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis. The methodology used is based on a cross-sectional study in patients receiving hemodialysis at the Centro Nacional de Salud Renal. Severe pruritus was defined as a score on the visual analogue scale greater than or equal to 7, and the strength of association with the possible risk factors was assessed by calculating prevalence ratios. Regarding the results, 264 patients were included, 59.9% were male, with a mean time on hemodialysis of 10.26 ± 7.14 years. 75% experienced pruritus, of this group, 1 in 3 presented severe pruritus. Hyperphosphatemia and the use of antihistamines were associated with a higher prevalence of severe pruritus (RP 1.71, 95% CI 1.09-267 and RP 2.39, 95% CI 1.51-3.75, respectively). The positive serology for Hepatitis C Virus was described as a protective factor for presenting severe pruritus (RP 0.55, 95% CI 0.33 - 0.89). In conclusion, severe uremic pruritus is a frequent problem in patients with chronic terminal kidney disease who have hyperphosphatemia and treatment with antihistamines independently of the time they have been on hemodialysis. / Revisión por pares

A partir de l’hémodialyse, nous étudierons certains problèmes plus généralement liés à la maladie chronique mais aussi la fin de vie pour mettre en tension trois dualités : l’exactitude et la vérité, les morales déontologiques et téléologiques, et la logique d’équivalence et de surabondance. Dans la maladie chronique, nous nous intéresserons aux cas où il existe une contradiction entre le devoir thérapeutique du médecin et la volonté de la personne malade. Nous montrerons que ces refus de soin en dialyse sont sous-tendus par une tension entre l’exactitude technique des traitements proposés et la vérité éthique et existentielle de la personne. Dans la fin de vie, nous nous poserons la question de savoir quand commence l’obstination déraisonnable, comment définir sa limite, et comment limiter ou arrêter la dialyse tout en étant certain de ne pas réaliser un homicide ? Nous montrerons également que les normes, les indicateurs et les protocoles prolifèrent pour participer à une standardisation des pratiques de plus en plus hégémonique, où plusieurs moteurs sont à l’œuvre, comme la rationalité néolibérale et la gestion du risque.  Ceci aboutit à un désenchantement des soignants. Un constat apparait : l’exactitude, la technique, les morales déontologiques rabattues sous forme de protocoles et la logique d’équivalence deviennent envahissantes. A l’inverse la vérité du sujet, l’éthique, la responsabilité de l'autre vulnérable, le don d’hospitalité tendent à être précarisés. La riposte à cette dérive pourrait être la réhabilitation de la singularité du sujet et la création de métaphore vive entre exactitude technique et la vérité éthique. Enfin, nous montrerons comment lorsqu’il existe un dilemme lié à une tension entre technique et éthique, la mise en place d’une réunion d’éthique nous a permis d’apporter la réponse la plus humaine possible et de favoriser le développement d’une culture d’équipe. / From hemodialysis, we will study certain problems more generally related to chronic disease but also to the end of life bring out the tension between three dualities: the accuracy and the truth, déontological and teleological ethics, and the logics of equivalence and superabundance. In chronic illness, we will be interested in cases where there is a contradiction between the medical duty of the physician and the will of the sick person. We will show that these refusals of care in dialysis are underpinned by a tension between the technical accuracy of the proposed treatments and the ethical and existential truth of the person. In the end of life, we will ask ourselves the question of when unreasonable obstinacy begins, how to define its limit, and how to limit or stop dialysis while being sure not to perform a homicide? We will also show that norms, standards, indicators and protocols proliferate to participate in a standardization of increasingly hegemonic practices, where several drivers are at work, such as neoliberal rationality and risk management. This leads to a disenchantment of caregivers. One observation emerges: the accuracy, the technique, the déontological ethics folded in the form of protocols and the logic of equivalence become invasive. Conversely, the truth of the subject, ethics, the responsibility of the other vulnerable, the gift of hospitality tend to be precarious. The response to this drift could be the rehabilitation of the singularity of the subject and the creation of a metaphor between technical accuracy and ethical truth. Finally, we will show how, when there is a dilemma linked to a tension between technique and ethics, the setting up of an ethics meeting allowed us to provide the most humane answer possible and to foster the development of a team culture.

No description available.

No description available.

Patients on peritoneal dialysis (PD) are reliant on the peritoneum to provide a semi-permeable barrier to allow for dialysis (solute clearance), salt and water removal (ultrafiltration). PD patients are at risk of developing peritoneal fibrosis and angiogenesis which can lead to a decline in peritoneal membrane function. Specifically, PD patients develop increased solute transport and decreased osmotic conductance leading to ultrafiltration failure. Peritoneal angiogenesis is the leading factor that results in augmented peritoneal membrane solute transport which is associated with worse outcomes – increased risk of mortality and PD technique failure. Transforming growth factor beta (TGFB) is one of the primary cytokines involved in inducing epithelial to mesenchymal transition (EMT) and fibrosis. We hypothesize that PD leads to injury of the epithelial lining of the peritoneum – the mesothelial cells. These cells undergo a transition process and transitioned mesothelium are a source for angiogenic and fibrogenic growth factors. Matrix Metalloproteinase (MMP) 9 is an angiogeneic factor and has been observed to correlate with increased expression of vascular endothelial growth factor (VEGF). MMP9 has the ability to cleave and activate membrane bound factors such as E-cadherin and b-catenin respectively. There is substantial evidence that the canonical WNT/b-catenin pathway is active during fibrosis, and angiogenesis in different biological contexts. Thus, we investigated the role of MMP9 and WNT signaling in peritoneal angiogenesis. Limited evidence exists describing the role of noncanonical WNT signaling but some reports suggest that non-canonical WNT signaling inhibits WNT/b-catenin signaling. Non-canonical WNT5A has differential effects based on receptor context and has been shown to block WNT/b-catenin signaling in the presence of Receptor Tyrosine Kinase Like Orphan Receptor 2 (Ror2). The overall hypothesis of this PhD thesis is that MMP9 and WNT signaling play a key role in inducing peritoneal angiogenesis and are associated with changes in peritoneal membrane function. We expect WNT5A and Ror2 to protect against peritoneal membrane injury. From the overnight effluent of stable PD patients, we cultured mesothelial cells and assayed these for expression of MMP and WNT related genes. MMP9 and WNT1 gene expression were observed to be strongly correlated with peritoneal membrane solute transport in patients on PD. WNT2 mRNA was also positively correlated with peritoneal solute transport. We overexpressed MMP9 in the mouse peritoneum to demonstrate its role in angiogenesis and confirmed these findings using MMP9 -/- mice. In addition to this, we have shown a novel mechanism by which MMP9 induces angiogenesis by E-cadherin cleavage and b-catenin mediated signaling. The observed cross-talk between MMP9 and b-catenin prompted investigation of the activation of canonical WNT/b-catenin signaling in development of peritoneal membrane injury. In an experimental model of TGFB induced pertioneal injury, we confirmed the activation of WNT/b-catenin signaling. In addition to this we, we blocked the WNT pathway and observed that WNT/b-catenin signaling is required to induce peritoneal angiogenesis. WNT5A mRNA was downregulated during TGFB induced injury suggesting a more protective role. Furthermore, several studies have demonstrated its ability to antagonize the WNT/b-catenin signaling pathway. We demonstrated that WNT5A protected against angiogenesis by blocking the canonical WNT pathway. WNT5A is thought to antagonize the WNT/b-catenin signaling pathway by signaling through receptor Ror2. In cell culture, we overexpressed TGFB and blocked Ror2. This resulted in elevated levels of VEGF and fibronectin suggesting that Ror2 is involved in mediating protection. Therefore, Ror2 possesses the ability to regulate VEGF and may be a potential candidate by which WNT5A mediates its protective effects. In conclusion, our findings identified MMP9 and WNT1 as potential biomarkers of increased peritoneal solute transport in patients that are on PD. We have also found a novel mechanism by which MMP9 interacts with b-catenin to induce peritoneal angiogenesis and have provided a first look at WNT/b-catenin signaling in peritoneal angiogenesis. Lastly, we have shown WNT5A to protect against peritoneal angiogenesis. Taken together, our findings are not only significant to the realm of PD research but hold wide applicability to research in the biomedical sciences. / Thesis / Doctor of Philosophy (PhD)

Bakgrund: Kronisk njursvikt är en diagnos som kräver livslång behandling. Peritonealdialys är en form av behandling som patienter sköter självständigt i hemmet och är en komplex vård. För att sjuksköterskan ska kunna ge god omvårdnad till denna patientgrupp är det viktigt att sjuksköterskan har förståelse för patienternas upplevelse av att leva med peritonealdialys behandling.Syfte: Syftet var att beskriva patienters upplevelser av att leva med peritonealdialys behandling.Metod: En allmän litteraturöversikt med en induktiv ansats som genomfördes med stöd av 11 resultatartiklar. Resultat: Ur resultatet framkom två huvudkategorier: erfarenhet av egenvård och inverkan på det vardagliga livet.Konklusion: Peritonealdialys behandling leder till en livsomvälvande omställning i livet för individen som drabbas av kronisk njursvikt. Ansvaret över sin hälsa blir en livsstil som behöver anpassas efter behandlingen. Genom dessa erfarenheter kan resultatet bidra till en ökad inblick och förståelse för hur vården kan anpassas för dessa patienter. / Background: Chronic kidney failure is a diagnosis that requires lifelong treatment. Peritoneal dialysis is a form of treatment that patients manage independently at home and is a complex treatment. In order for the nurse to be able to provide good care to this patient group, it is important that the nurse has an understanding of the patients' experience of living with peritoneal dialysis treatment.  Purpose: The purpose was to describe patients' experiences of living with peritoneal dialysis treatment.  Method: A general literature review with an inductive approach was carried out with the support of 11 results articles.  Results: Two main categories emerged from the results: experience of selfcare and impact on everyday life.  Conclusion: Peritoneal dialysis treatment leads to a life-changing adjustment in the life of the individual who suffers from chronic kidney failure. Responsibility for one's health and treatment becomes a lifestyle that needs to be adapted to the care. Through these experiences, the results can contribute to an increased insight and understanding of how care can be adapted for these patients.

Las personas con Enfermedad Renal Crónica tratadas con hemodiálisis pueden sufrir complicaciones durante su proceso de enfermedad que pueden prevenirse mediante la promoción de la salud; así que enfermería es clave para educar al paciente y mejorar su autocuidado según las necesidades de cada uno, mejorando su calidad de vida. La actual investigación secundaria lleva por título: “Intervenciones de enfermería para promover el autocuidado del paciente sometido a hemodiálisis”, con el objetivo de determinar la intervención de enfermería para promover el autocuidado del paciente sometido a hemodiálisis. Se utilizó la práctica de enfermería basada en la evidencia; con el esquema "PIS" se diseñó la pregunta clínica: ¿Cuál es la intervención de enfermería en el autocuidado del paciente en hemodiálisis? La búsqueda se efectuó en bases de datos como: PubMed, BVS, Google Académico, Scielo, Epistemonikos, Ciencia Digital, hallándose 200 artículos de investigación, tras la cual se emplearon criterios de inclusión y exclusión; quedando 10 artículos que estaban sujetas a la Guía de validez y eficacia de Gálvez Toro, salvo un estudio que se examinó con la revisión crítica de CASPE, obteniéndose un nivel de evidencia de 3 y un grado de recomendación C. En repuesta a la pregunta clínica la intervención de enfermería cumple un rol importante dirigido a orientarlos, ayudando a mejorar su autocuidado de manera positiva y así lograr disminuir posibles complicaciones que puedan tener durante su proceso. / People with CKD treated with hemodialysis may suffer complications during their disease process that can be prevented through health promotion; so nursing is key to educate the patient and improve their self-care according to the needs of each one, improving their quality of life. The current secondary research is entitled: “Nursing interventions to promote hemodialysis patient's self-care”, with the objective of determining the nursing intervention to promote hemodialysis patient's self-care. Evidence-based nursing practice was used; with the “PIS” scheme, the clinical question was designed: What is the nursing intervention in the self-care of the hemodialysis patient? The search was carried out in databases such as: PubMed, BVS, Google Scholar, Scielo, Epistemonikos, Digital Science, finding 200 research articles, after which inclusion and exclusion criteria were used; leaving 10 articles that were subject to the validity and efficacy Guide of Gálvez Toro, except for one study that was examined with the critical review of CASPE, obtaining a level of evidence of 3 and a grade of recommendation C. In response to the clinical question, the nursing intervention fulfills an important role aimed at orienting them, helping to improve their self-care in a positive manner, thus reducing possible complications they may have during their process.

Background: Simultaneous pancreas-kidney transplantation (SPKT) profoundly improves the health-related quality of life (HRQoL) of recipients. However, the influence of the pre-transplant dialysis modality on the success of the SPKT and post-transplant HRQoL remains unknown. Methods: We analyzed the surgical outcome, long-term survival, as well as HRQoL of 83 SPKTs that were performed in our hospital between 2000 and 2016. Prior to transplant, 64 patients received hemodialysis (HD) and nineteen patients received peritoneal dialysis (PD). Physical and mental quality of life results from eight basic scales and the physical and mental component summaries (PCS and MCS) were measured using the Short Form 36 (SF-36) survey. Results: Peri- and postoperative complications, as well as patient and graft survival were similar between the two groups. Both groups showed an improvement of HRQoL in all SF-36 domains after transplantation. Compared with patients who received HD before transplantation, PD patients showed significantly better results in four of the eight SF-36 domains: physical functioning (mean difference HD - PD: - 12.4 ± 4.9, P = < 0.01), bodily pain (- 14.2 ± 6.3, P < 0.01), general health (- 6.3 ± 2.8, P = 0.04), vitality (- 6.8 ± 2.6, P = 0.04), and PCS (- 5.2 ± 1.5, P < 0.01) after SPKT. In the overall study population, graft loss was associated with significant worsening of the HRQoL in all physical components (each P < 0.01). Conclusions: The results of this analysis show that pre-transplant dialysis modality has no influence on the outcome and survival rate after SPKT. Regarding HRQoL, patients receiving PD prior to SPKT seem to have a slight advantage compared with patients with HD before transplantation.

La maladie rénale chronique (MRC) induit des anomalies du métabolisme phosphocalcique, avec des conséquences à la fois osseuses, vasculaires et biologiques. La prise en charge optimale de ces désordres représente un challenge quotidien pour le néphrologue pédiatre, à la fois sur le court terme (équilibre biologique) et sur le long terme (prévention des fractures, optimisation de la croissance et limitation de l’apparition des calcifications vasculaires). Peu d’outils sont actuellement disponibles pour évaluer ces atteintes, et de nouveaux outils prometteurs, à la fois biologiques (FGF23) et radiologiques (HR-pQCT) apparaissent. Néanmoins, les données pédiatriques sur ces outils restent rares. Cette thèse de doctorat a permis d’évaluer ces nouveaux moyens chez ces enfants MRC, notamment en évaluant l’HR-pQCT dans cette population, et en déterminant des valeurs de référence du FGF23 en fonction de l’âge, du sexe et de la fonction rénale. Nous avons pu aussi montrer que les concentrations circulantes de FGF23 ne sont pas dépendantes du sexe dans une population pédiatrique, mais qu’elles augmentent avec l’âge et l’indice de masse corporelle, mais aussi en cas d’antécédent de transplantation d’organe solide ou de traitement par corticostéroïdes. D’un point de vue plus fondamental, nous avons pu montrer que dans des monocytes issus de donneurs sains, une exposition au FGF23 induit une diminution de l’expression des 2 enzymes principales impliquées dans le métabolisme de la vitamine D (1α hydroxylase et 24 hydroxylase), en induisant également une diminution du peptide antimicrobien cathélicidine. Ces résultats permettent donc de décrire un nouveau rôle pour le FGF23 dans la régulation de l’immunité innée / Chronic kidney disease can induce mineral and bone disorders (CKD-MBD), with deleterious consequences for bone and vessels. The management of such abnormalities can be challenging, from the daily biological balance between calcium, phosphorus and PTH levels, to the long-term prevention of morbidities such as fractures, growth impairment and vascular calcifications. Some tools can help to accurately assess CKD-MBD, e.g., new bone imaging techniques (HR-pQCT) and FGF23, but they are rarely used in pediatric populations. In addition to evaluating HR-pQCT in CKD children and healthy controls, this PhD thesis allowed us to determine reference values for circulating FGF23 levels depending on age, gender and renal function; we also showed that FGF23 levels increased not only with age and BMI, but also in cases of solid organ transplant or corticosteroids therapy. We have also showed in vitro that FGF23 could inhibit the two key enzymes of vitamin D metabolism (1α hydroxylase et 24 hydroxylase) in monocytes issued from healthy donors, with in turn a decreased synthesis of the antimicrobial cathelicidin. These later results highlight a new role for FGF23 in innate immunity, and may bring new insights in the understanding of FGF23 deregulation during CKD

O carvedilol é um fármaco utilizado na terapêutica da hipertensão e da insuficiência cardíaca congestiva. É disponível para uso clínico como racemato e seus enantiômeros apresentam atividade semelhante sobre os receptores 1-adrenérgicos, sendo que o enantiômero S-(-) é mais ativo como antagonista dos receptores adrenérgicos. O presente estudo visa investigar a influência do Diabetes mellitus (DM) tipo 2 e da insuficiência renal crônica (IRC) em pacientes em diálise peritoneal ambulatorial contínua (DPAC) na farmacocinética enantiosseletiva e na farmacodinâmica do carvedilol em pacientes hipertensos. Os pacientes hipertensos investigados divididos nos grupos controle (n=8), DM tipo 2 (n=8) e IRC em DPAC (n=6) receberam dose única p.o. de 25 mg de carvedilol racêmico. Os enantiômeros do carvedilol e metabólitos 4-hidroxifenil e O-desmetilcarvedilol foram analisados no sistema LC-MS/MS empregando coluna quiral e fase móvel constituída por mistura de metanol: ácido acético: dietilamina. O método foi linear no intervalo de concentrações de 0,1-100 ng de cada enantiômero do carvedilol/mL de líquido de diálise, 0,2-200 ng de cada enantiômero do carvedilol/mL de plasma, 2,5-2500 ng de cada enantiômero do carvedilol, 4-hidroxifenil e O-desmetilcarvedilol/mL de urina. Os parâmetros farmacocinéticos foram calculados empregando o programa WinNonlin. O teste de Wilcoxon foi usado para avaliar as razões enantioméricas dentro dos grupos e o teste de Mann-Whitney foi utilizado para avaliar as diferença dos parâmetros farmacocinéticos entre os grupos. Na investigação do fenótipo oxidativo tipo metoprolol todos os pacientes incluídos no estudo foram fenotipados como metabolizadores extensivos. Os pacientes investigados com DM tipo 2 comparados com o grupo controle não apresentaram alterações na farmacocinética e farmacodinâmica (PK-PD) do carvedilol. Os pacientes com IRC em DPAC apresentaram valores de clearance (CL/F) dos enantiômeros R-(+) - e S-(-)-carvedilol de 25,17 e 27,89 L/h, respectivamente, sendo significativamente inferiores aos obtidos para os pacientes do grupo controle (76,76 e 142,0 L/h). As razões de AUCR/S foram de 2,27 para os pacientes do grupo controle e de 0,97 para os pacientes com IRC em DPAC. Os pacientes com IRC em DPAC não mostraram enantiosseletividade na farmacocinética do carvedilol em razão do acúmulo plasmático preferencial do enantiômero com atividade -bloqueadora S-(-)-carvedilol. / Carvedilol is used for the treatment of hypertension and congestive heart failure. The drug is available for clinical use as the racemate and its enantiomers exert similar activity on 1-adrenergic receptors, whereas the S-(-) enantiomer is more active as a -adrenergic receptor antagonist. The aim of the present study was to investigate the influence of type 2 Diabetes mellitus (DM) and chronic renal failure (CRF) on patients receiving continuous ambulatory peritoneal dialysis (CAPD) on the enantioselective pharmacokinetics and pharmacodynamics of carvedilol in hypertensive patients. The hypertensive patients were divided into a control (n=8), type 2 DM (n=8) and CRF on CAPD (n=6) group and received a single oral dose of 25 mg racemic carvedilol. The enantiomers of carvedilol and of the metabolites 4-hydroxyphenyl and O-desmethylcarvedilol were analyzed by LC-MS/MS using a chiral column and a mobile phase consisting of a mixture of methanol:acetic acid-diethylamine. The method was linear within the following concentration ranges: 0.1-100 ng of each carvedilol enantiomer/mL dialysis fluid, 0.2-200 ng of each carvedilol enantiomer/mL plasma, and 2.5-2500 ng of each enantiomer of carvedilol, 4-hydroxyphenyl carvedilol and O-desmethyl carvedilol/mL urine. The pharmacokinetic parameters were calculated using the WinNonlin program. Enantiomer ratios within groups were evaluated by the Wilcoxon test and the Mann-Whitney test was used to determine differences in the pharmacokinetic parameters between groups. Determination of the metoprolol type oxidation phenotype showed that all patients included in the study were extensive metabolizers. Patients with type 2 DM presented no changes in the pharmacokinetics or pharmacodynamics of carvedilol when compared to the control group. Clearance (CL/F) of the R-(+)- and S-(-)-carvedilol enantiomers was significantly lower in patients with CRF on CAPD (25.17 and 27.89 L/h, respectively) compared to the control group (76.76 and 142.0 L/h). The AUCR/S ratios were 2.27 for control patients and 0.97 for patients with CRF on CAPD. Patients with CRF on CAPD showed no enantioselectivity in the pharmacokinetics of carvedilol due to the preferential plasma accumulation of the enantiomer with -blocker activity, S-(-)-carvedilol.