L'impact de l'activité physique sur la situation économique des individus

Rapport de recherche présenté à la Faculté des arts et des sciences en vue de l'obtention du grade de Maîtrise en sciences économiques

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease

Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients

Treatment with Glucocorticoids or Calcineurin Inhibitors in Primary FSGS

In primary FSGS, calcineurin inhibitors have primarily been studied in patients deemed resistant to glucocorticoid therapy. Few data are available about their use early in the treatment of FSGS. We sought to estimate the association between choice of therapy and ESRD in primary FSGS

The role of calcineurin inhibitor therapy in treatment of primary focal segmental glomerulosclerosis

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in adults. Glucocorticoids have been studied as treatment of primary FSGS in retrospective studies. Although some studies evaluated the role of calcineurin inhibitors (CNIs) in a steroid-resistant primary FSGS population, their role as early therapy remains poorly established. OBJECTIVES: To evaluate the efficacy of CNIs in treatment of primary FSGS.METHODS: Two studies were performed. The first was a systematic review to describe the efficacy of CNIs compared to placebo, supportive therapy and other immunosuppressive agents. The second study used registry data and time-dependent Cox models to compare time to end-stage kidney disease (ESKD) between different immunosuppressive therapies while controlling for potential confounders, including those influencing choice of therapy and renal survival.RESULTS: Study 1: Six randomized controlled trials and 2 cohort studies were reviewed. All but one suggested CNIs may be beneficial in steroid-resistant primary FSGS compared to placebo or supportive therapy. No prospective trial studied the efficacy of calcineurin inhibitors in first-line treatment of FSGS. Study 2: In adjusted Cox regression, immunosuppressive therapy with glucocorticoids and/or CNIs was associated with a better renal survival [hazard ratio 0.49 (95% confidence interval 0.28, 0.86)] than no therapy. Although not statistically significant, CNIs ± glucocorticoids were associated with a lower likelihood of ESKD [hazard ratio 0.42 (95% confidence interval 0.15, 1.18)] than glucocorticoids alone.CONCLUSIONS: Our results suggest that immunosuppressive therapy with CNIs and/or glucocorticoids is associated with better renal survival compared with supportive therapy alone in patients with FSGS. Whether early use of CNIs alone or in combination with glucocorticoids are superior to glucocorticoids alone in attaining remission and preventing ESKD, remains to be established.CONTEXTE : L’hyalinose focale et segmentaire (HFS) primaire est la cause la plus commune de syndrome néphrotique chez l’adulte. Les glucocorticoïdes ont été étudiés comme traitement de première ligne dans l’HFS primaire dans des études rétrospectives. Malgré le fait que des études ont évalué le rôle des inhibiteurs de la calcineurine (ICN) dans une population d’HFS primaire résistante aux stéroïdes, leur rôle comme thérapie au début de l’évolution de la maladie reste mal établi.OBJECTIFS : Évaluer l’efficacité des ICN dans le traitement de l’HFS.MÉTHODE : Deux études ont été conduites. La première était une revue systématique pour décrire l’efficacité des ICN par rapport à un agent placebo, à un traitement non-immunologique, ainsi qu’à d’autres agents immunosuppresseurs. Dans la deuxième étude, nous avons utilisé les données d’un registre et des modèles de régression de Cox afin de comparer le temps à l’insuffisance rénale terminale (IRT) entre différents traitements immunosuppresseurs et ce, en ajustant pour des facteurs confondants potentiels, incluant ceux connus pour influencer le choix du traitement et l’issue rénale.RÉSULTATS : Étude 1 : Six essais cliniques randomisés et 2 études de cohorte ont été revus. Tous les articles sauf un suggèrent un effet bénéfique des ICN dans l’HFS primaire résistante à la corticothérapie. Aucune étude prospective n’a évalué l’efficacité des ICN dans le traitement de première intention de l’HFS. Étude 2 : Dans la régression de Cox ajustée, l’immunosuppression avec des glucocorticoïdes avec ou sans ICN est associée à une meilleure survie rénale [rapport risque 0.49 (intervalle de confiance à 95% 0.28, 0.86)] qu’une absence d’immunothérapie. Quoique qu’il ne soit pas statistiquement significatif, les ICN ± glucocorticoïdes sont associés à un risque moindre d’IRT [rapport risque 0.42 (intervalle de confiance à 95% 0.15, 1.18)] que les glucocorticoïdes seuls.CONCLUSIONS : Nos résultats suggèrent qu’un traitement immunosuppresseur composé d’un ICN avec glucocorticoïdes, ou de glucocorticoïdes seuls est associé à une meilleure survie rénale qu’une thérapie de support seule chez les patients atteints d’HFS. La supériorité des ICN avec ou sans glucocorticoïdes vis-à-vis les glucocorticoïdes seuls pour induire une rémission ou prévenir l’IRT reste indéterminée

MFG-E8 Released by Apoptotic Endothelial Cells Triggers Anti-Inflammatory Macrophage Reprogramming

Apoptotic endothelial cells are an important component of the ‘‘response to injury’ ’ process. Several atherosclerosis risk factors such as hyperglycemia and oxidized low-density lipoproteins, and immune injuries, such as antibodies and complement, induce endothelial cell apoptosis. While endothelial cell apoptosis is known to affect neighboring vascular wall cell biology, its consequences on macrophage reprogramming are ill defined. In this study, we report that apoptosis of human and mouse endothelial cells triggers the release of milk fat globule-epidermal growth factor 8 (MFG-E8) and reprograms macrophages into an anti-inflammatory cells. We demonstrated that MFG-E8 is released by apoptotic endothelial cells in a caspase-3-dependent manner. When macrophages were exposed to conditioned media from serumstarved apoptotic endothelial cells, they adopt a high anti-inflammatory, low pro-inflammatory cytokine/chemokine secreting phenotype that is lost if MFG-E8 is absent from the media. Macrophage treatment with recombinant MFG-E8 recapitulates the effect of conditioned media. Finally, we showed that MFG-E8-mediated reprogramming of macrophages occurs through increased phosphorylation of signal transducer and activator of transcription-3 (STAT-3). Taken together, our study suggests a key role of MFG-E8 release from apoptotic endothelial cells in macrophage reprogramming an

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

Objective The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. Methods We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N -acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. Results Baseline serum creatinine was 57.8 ± 34.5 μmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. Conclusions Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function