Nutrients

The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut-brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case-control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.COGINUT : Cognition, anti-oxydants, acides gras: approche interdisciplinaire du rôle de la nutrition dans le vieillissement du cerveauHistoire naturelle du déclin cognitif et du besoin de soins chez le sujet âg

Social Deprivation Is Associated With Lower Access to Pre-emptive Kidney Transplantation and More Urgent-Start Dialysis in the Pediatric Population

Introduction Socioeconomic status (SES) is recognized as an important determinant of kidney health. We aimed to evaluate the association of social deprivation with different indicators at kidney replacement therapy (KRT) initiation in the French pediatric metropolitan population. Methods All patients with end-stage kidney disease (ESKD) who started KRT before 20 years old in France between 2002 and 2015 were included. We investigated different indicators at KRT initiation, which are as follows: KRT modality (dialysis vs. pre-emptive transplantation), late referral to a nephrologist, and dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD], urgent vs. planned start of dialysis, use of catheter vs. use of fistula for HD vascular access). An ecological index (European Deprivation Index [EDI]) was used as a proxy for social deprivation. Results A total of 1115 patients were included (males 59%, median age at dialysis 14.4 years, glomerular/vascular diseases 36.8%). The most deprived group represented 38.7% of the patients, suggesting pediatric patients with ESKD come from a more socially deprived background. The most deprived group was more likely to initiate KRT with dialysis versus kidney transplantation. Among patients on HD, the odds of starting treatment in emergency with a catheter was >2-fold higher for the most deprived compared with the least deprived children (adjusted odds ratio [aOR] 2.35, 95% CI 1.16–4.78). Conclusion Children from the most deprived area have lower access to pre-emptive transplantation, have lower access to PD, tend to be late referred to a nephrologist, and have more urgent initiation of HD with a catheter

Social inequalities in health in young people with chronic kidney disease

La maladie rénale chronique (MRC) correspond à des dommages structurels des reins qui conduisent à une réduction progressive et anormale des fonctions rénales. Ces fonctions d’épuration, de régulation et de sécrétion d’hormones sont vitales et leurs dégradations peuvent être fatales. Cette maladie s’aggrave de façon inéluctable à travers cinq stades et est irréversible. Une fois atteint le stade 5 ou « terminal » de la MRC (insuffisance rénale terminale, IRT), il est nécessaire de mettre en place un traitement de suppléance : la dialyse ou la transplantation d’un nouveau rein. On parle alors d’IRT traité (IRTT). Alors que la MRC à différents stades pourrait toucher 5 à 10% de la population française adulte, et comprenait près de 90 000 patients en IRTT en 2018, cette maladie est rare au sein de la population pédiatrique, avec environ 930 enfants en IRTT en 2018. Cependant, ses conséquences peuvent être majeures puisqu’elle impacte le développement physique et psychosocial de l’enfant (retard de croissance, dénutrition, problèmes cognitifs…). Ainsi, les objectifs des soignants, personnels de santé et chercheurs sont de ralentir la progression de la maladie vers le stade terminal, et une fois atteint, d’optimiser les traitements de suppléance pour assurer la meilleure prise en charge possible et une meilleure qualité de vie aux patients. Dans ce contexte, étudier les inégalités sociales de santé peut se révéler pertinent pour aider à l’élaboration d’interventions mieux ciblées à chaque population. Cependant, chez l’enfant, le lien entre des facteurs sociaux comme le revenu, le niveau d’éducation ou encore le contexte familial et la MRC n’est que très peu exploré. A notre connaissance, aucune étude n’a été réalisée en Europe sur l’impact de la défavorisation sociale sur le parcours de soins, les modalités et les résultats de prise en charge à différents stades de la MRC pédiatrique. Or, en Europe et en France plus particulièrement, le système de santé mis en place mais également les aides sociales proposées ne sont pas les mêmes qu’aux Etats-Unis ou dans les pays à ressources limitées dans lesquels des associations ont été mises en évidence. Il est donc important d’évaluer si les résultats observés dans ces pays sont superposables à la France pour adapter la prise en charge des enfants et adolescents. L’objectif de cette thèse est donc d’étudier les inégalités sociales de santé dans la MRC pédiatrique et plus précisément d’évaluer l’association entre la défavorisation et l’évolution de l’IRTT chez des enfants et adolescents. Pour répondre à cet objectif, nous avons utilisé des données de patients âgés de moins de 20 ans entre 2002 et 2015, issues du registre national REIN, recueillant les informations de tous les patients initiant un traitement de suppléance par dialyse ou greffe rénale. En l’absence d’indicateurs individuels, la défavorisation sociale a été estimée à l’aide d’un indicateur écologique appliqué à l’adresse de résidence des enfants, l’European Deprivation Index, score continu catégorisable en cinq groupes : le quintile 1 correspondant aux zones géographiques les plus favorisées et le quintile 5 aux zones les plus défavorisées du pays. Nous avons ainsi étudié l’association entre l’EDI et 1) l’incidence de l’IRTT pédiatrique en France, 2) des indicateurs de prise en charge et conditions cliniques à l’initiation de la dialyse, puis 3) la survie du greffon et du patient chez les jeunes transplantés rénaux. Les résultats principaux de cette thèse sont que, chez les patients issus de milieux les plus défavorisés, l’incidence de l’IRTT était plus élevée, le traitement de suppléance était plus tardif, plus souvent effectué en urgence et en hémodialyse et que l’échec de transplantation rénale état plus fréquent. Nous pensons que l’étude de cette association avec différents critères de l’IRTT est importante pour proposer des prises en charge ciblées pour cette population.Chronic Kidney Disease (CKD) is a structural damage to the kidneys that leads to a progressive and abnormal reduction of kidney function. These functions of blood purification, regulation and secretion of hormones are vital and their degradation can be fatal. This disease inevitably worsens through five stages of CKD and is irreversible. Once stage 5 or end-stage kidney disease (ESKD) is reached, it is necessary to implement a kidney replacement therapy: dialysis or transplantation of a kidney graft. While CKD at different stages could affect 5 to 10% of the French adult population, and include nearly 90,000 patients treated for ESKD in 2018, the disease is rare in the pediatric population, with approximately 930 children treated for ESKD in 2018. However, its consequences can be major since it impacts the physical and psychosocial development of children (growth delay, undernutrition, cognitive problems, social adjustment, etc.). Thus, the objectives of caregivers, healthcare professionals and researchers are to slow the progression of the disease towards ESKD, and once reached, to optimize kidney replacement therapy to ensure the best possible care and a better quality of life for patients. In this context, the study of social inequalities in health may be relevant to help develop targeted interventions to each population. However, in children, the link between social factors such as income, level of education, or family context and CKD has been little investigated. To our knowledge, no study has been carried out in Europe on the impact of social deprivation on the care pathway, modalities and outcomes of kidney care at different stages of the pediatric CKD. However, in Europe, and in France in particular, the healthcare system in place, as well as the social assistance offered, is not the same as in the USA or in countries with limited resources, where associations have been identified. It is therefore important to evaluate whether the results observed in these countries are reproducible and applicable in France in order to adapt kidney care of children and adolescents. The objective of this thesis is therefore to study social inequalities in the pediatric CKD population and more specifically to evaluate the association between deprivation and the outcomes of the ESKD in children and adolescents. To meet this objective, we used data from patients aged less than 20 years who initiated kidney replacement therapy between 2002 and 2015, from the national registry REIN that collects information from all patients treated by dialysis or kidney transplantation. In the absence of individual factors, social deprivation was estimated using an ecological indicator applied to the children's home address, the European Deprivation Index, a continuous score that can be categorized into five quintiles: quintile 1 corresponding to the least deprived geographical areas and quintile 5 to the most deprived areas of the country. We thus studied the association between EDI and 1) the incidence of pediatric treated ESKD in France, 2) practice patterns and clinical conditions at dialysis initiation, and 3) graft and patient survival in young kidney transplant recipients. The main results of this thesis are that in patients from the most deprived areas, the incidence of treated ESKD was higher, kidney replacement therapy was initiated later, was more frequently started in emergency and by hemodialysis, and that kidney transplant failure was more likely. Our data suggests that studying different outcomes of ESKD is important to subsequently propose targeted management for this population

Eur J Pediatr

To describe healthcare professionals' perceptions of social health inequalities in the context of pediatric chronic disease and their insights regarding proportionate universalism as a potential solution to reduce them. Semi-directive interviews were conducted with healthcare professionals from different pediatric chronic disease departments of a single French academic hospital. This qualitative study was based on an inductive thematic analysis; an interview topic guide was used for the interviews and the analysis. In this study, we highlighted three main themes: the healthcare professionals' perceptions of social health inequalities in their practices, their beliefs regarding the causality of those inequalities, and potential solutions proposed by healthcare professionals to reduce them. Healthcare professionals very often associated inequalities with socio-economic precariousness or geographical disparities but were not familiar with the notion of a social gradient. Paradoxically, while they claimed not to differentiate among patients in their practice, they did report adapting care, depending on the social situation. For healthcare professionals, inequalities were the result of misunderstood problems, a lack of family support, a failure of the prevention system, and a lack of financial resources. CONCLUSION: We still need to develop solutions to tackle those inequalities at every level of the healthcare system, and healthcare professionals must be more actively involved in this effort. One approach is to adapt public health principles such as proportionate universalism to individual care. WHAT IS KNOWN: • Social health inequalities exist in pediatric care and a social gradient has been shown in many clinical situations. • Exploring health professionals' perceptions of social health inequalities can lead to solutions to tackle them. WHAT IS NEW: • Pediatricians and pediatric nurses were not fully aware of the social gradient of health. • Although they claimed not to differentiate between patients in their practice, healthcare professionals did adapt care when complicated social situations arose

Kidney Int

Socioeconomic status is an important determinant of health. Its impact on kidney transplantation outcome has been studied among adults but data in children are scarce, especially in Europe. Here, we investigate the association between the level of social deprivation (determined by the continuous score European Deprivation Index) and graft failure risk in pediatric kidney transplant recipients. All patients listed under 18 years of age who received a first kidney transplant between 2002 and 2014 in France were included. Of 1050 kidney transplant recipients (males 59%, median age at transplantation 13.2 years, preemptive transplantation 23%), 211 graft failures occurred within a median followup of 5.9 years. Thirty-seven percent of these patients belong to the most deprived quintile, suggesting that deprivation is more frequent in pediatric patients with end-stage kidney disease (ESKD) than in the general population. Five- and ten-year graft survival were 85% and 69%, respectively, in the most deprived quintile vs. 90% and 83%, respectively, in the least deprived quintile. At any time after transplantation, patients in the most deprived quintile had almost a two-fold higher hazard of graft failure compared with the least deprived quintile, after adjustment for age at renal replacement therapy, duration of dialysis, primary kidney disease, and rural/urban living environment (hazard ratio 1.99; 95% confidence interval 1.20-3.28). The hazard of graft failure did not differ significantly between girls and boys. Thus, our findings suggest a lower socioeconomic status is independently associated with poor graft outcome in pediatric kidney transplantation