8 research outputs found
Effets non osseux de la vitamine D
Actuellement, la vitamine D doit ĂȘtre considĂ©rĂ©e comme une prohormone dont les effets dĂ©passent la prĂ©vention du rachitisme/ostĂ©omalacie. De nombreux tissus sont capables de convertir localement la 25-hydroxyvitamine D en calcitriol qui aura alors des actions auto/paracrines sur la prolifĂ©ration et la diffĂ©renciation cellulaires, lâapoptose, les sĂ©crĂ©tions dâinsuline et de rĂ©nine, la production dâinterleukines et la bactĂ©ricidie. Des donnĂ©es Ă©pidĂ©miologiques et expĂ©rimentales sont en faveur dâun rĂŽle protecteur de la vitamine D contre les cancers, le diabĂšte de type 2, les maladies cardiovasculaires, auto-immunes, infectieuses, rĂ©nales et le dĂ©ficit musculaire. Quelques Ă©tudes dâintervention confirment certains de ces effets
Implication du stress du rĂ©ticulum endoplasmique en transplantation dâorgane solide
Le stress du rĂ©ticulum endoplasmique (RE) est produit par lâaccumulation de protĂ©ines mal conformĂ©es dans le RE et conduit Ă lâactivation dâune rĂ©ponse adaptative, la rĂ©ponse UPR (unfolded protein response). Le stress du RE est impliquĂ© dans la pathogĂ©nie de nombreuses pathologies telles que la maladie dâAlzheimer, lâathĂ©rosclĂ©rose, les diabĂštes de types 1 et 2 ou certaines maladies inflammatoires du tube digestif. Des donnĂ©es expĂ©rimentales rĂ©centes suggĂšrent son implication en transplantation dâorgane solide. Lâobjet de cette revue est de synthĂ©tiser les donnĂ©es sur les mĂ©canismes molĂ©culaires du stress du RE et les consĂ©quences de celui-ci en pathologie, et plus particuliĂšrement Ă partir de plusieurs modĂšles de transplantation dâorganes solides et de lĂ©sions tissulaires dans lesquels le stress du RE peut ĂȘtre impliquĂ©. Nous discutons aussi les implications possibles du stress du RE, au-delĂ de la simple rĂ©ponse adaptative et de la rĂ©gulation de la mort cellulaire, sur les modifications des propriĂ©tĂ©s fonctionnelles et les changements phĂ©notypiques. La modulation de la rĂ©ponse UPR au cours du stress du RE en transplantation dâorgane solide pourrait constituer une cible thĂ©rapeutique prometteuse. La mise en Ă©vidence de marqueurs du stress du RE tels que BiP/GRP78 ou CHOP dans les biopsies de greffon pourrait permettre la dĂ©tection prĂ©coce dâun processus pathologique en cours avant que les lĂ©sions histologiques ne soient dĂ©finitivement Ă©tablies. Lâautre enjeu serait de trouver une stratĂ©gie pour bloquer la mort cellulaire causĂ©e par le stress du RE, ce qui fournit un champ dâinvestigation passionnant pour de futurs traitements protecteurs
Utilisation du fer en nĂ©phrologie : enquĂȘte sur les pratiques des nĂ©phrologues français
International audienceThe French-speaking Society of Nephrology, Dialysis and Transplantation conducted, in 2018, a survey among French nephrologists into their iron prescribing habits for patients with chronic kidney disease stages 3 to 5 before dialysis. The results show that 73% of nephrologists use intravenous iron before dialysis stage. When a patient has gastrointestinal symptoms under oral iron therapy, only 48% of nephrologists use intravenous route. The starting thresholds for iron are for 78% of nephrologists a transferrin saturation < 20% and for 80% a serum ferritin < 100 mu g/L. Only 14% start iron when a transferrin saturation < 25% or higher and 29% start iron when serum ferritin < 200 mu g/L or higher. High dosages of iron (500 and 1000 mg) are used by 58% of nephrologists. Finally, about 30% of nephrologists refer to various barriers to intravenous iron prescription, such as cost, unavailability of intravenous iron in their facility or lack of day hospital unit. The correction of iron deficiency without anemia remains controversial. It is performed by only 43% of nephrologists. These results show an improvement of the practices compared to a 2006 survey. However, they indicate a sub-prescription of iron compared to the European recommendations which recommend a starting threshold of iron of transferrin saturation < 25% and ferritinemia < 200 mu g/L in anemic patients not treated with erythropoietin-stimulating agents. (C) 2020 Societe francophone de nephrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved
[Current status of persistent chronic hyperkalaemia in France: An expert consensus based on a Delphi approach].
International audienceINTRODUCTION: In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed. METHODS: A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26~voting participants among 40~invited panellists in first round) and june 2020 (20~voting participants among 26 panellists in second round). RESULTS: Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage~3B to stage~5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins). CONCLUSIONS: The panel expressed a need for new treatment strategies validated by clinical trials
Trajectory of extracellular fluid volume over time and subsequent risks of end-stage kidney disease and mortality in chronic kidney disease: a prospective cohort study
International audienceBackground: Extracellular fluid volume (ECF) is independently associated with chronic kidney disease (CKD) progression and mortality in patients with CKD, but the prognostic value of the trajectory of ECF over time beyond that of baseline value is unknown. Objectives: To characterize ECF trajectory and evaluate its association with the risks of end-stage kidney disease (ESKD) and mortality. Methods: From the prospective tricentric NephroTest cohort, we included 1588 patients with baseline measured glomerular filtration rate (mGFR) â„15 mL minâ1/1.73 m2 and ECF measurement. ECF and GFR were measured repeatedly using the distribution volume and clearance of 51Cr-EDTA, respectively. ESKD and mortality were traced through record linkage with the national registries. Adjusted shared random-effect joint models were used to analyse the association between the trajectory of ECF over time and the two competing outcomes. Results: Patients were mean age 58.7 years, 66.7% men, mean mGFR of 43.6 ± 18.6 mL minâ1/1.73 m2 and mean ECF of 16.1 ± 3.6 L. Over a median follow-up of 5.3 [IQR: 3.0;7.4] years, ECF increased by 136 [95%CI 106;167] mL per year on average, whilst diuretic prescription and 24-hour urinary sodium excretion remained stable. ESKD occurred in 324 (20.4%) patients, and 185 (11.6%) patients died before ESKD. A higher current value of ECF was associated with increased hazards of ESKD (adjusted hazard ratio [aHR]: 1.12 [95%CI 1.06;1.18]; P < 0.001 per 1 L increase in ECF), and death before ESKD (aHR: 1.10 [95%CI 1.04;1.17]; P = 0.002). Conclusions: The current value of ECF was associated with the risks of ESKD and mortality, independent of multiple potential confounders, including kidney function decline. This highlights the need for a close monitoring and adjustment of treatment to avoid fluid overload in CKD patients
Vitamine D et rein
Le calcitriol et ses analogues inhibent le systÚme rénineangiotensine-
aldostérone, qui joue un rÎle important dans le
développement des lésions glomérulaires et tubulo-interstitielles
et dans lâapparition de la protĂ©inurie, mais aussi lâactivation de la
voie NF-kB qui est connue pour favoriser la maladie rénale
chronique en stimulant lâinflammation et la fibrogenĂšse.
Les effets pléiotropes de la vitamine D sont également trÚs
intéressants pour le patient insuffisant rénal (diminution de la
mortalité, de la protéinurie et effets anti-inflammatoires). De
plus, lâadministration de vitamine D native (cholĂ©calcifĂ©rol ou
ergocalciférol) diminue les concentrations sériques de parathormone.
La supplĂ©mentation en vitamine D native chez lâinsuffisant
rĂ©nal nâentraĂźne pas de toxicitĂ© ni dâaugmentation du risque
de calcification vasculaire malgré les effets hypercalcémiants et
hyperphosphorémiants de cette molécule sous sa forme active.
La vitamine D per se (câest-Ă -dire sans apports calciques
excessifs), aux doses habituellement utilisées en clinique,
nâest pas associĂ©e Ă une augmentation du risque de lithiase
urinaire.
Dans le domaine de la transplantation rénale, les études
expérimentales montrent un rÎle protecteur des analogues
de la vitamine D contre le rejet aigu, mais les Ă©tudes cliniques
restent Ă ce jour principalement observationnelles
Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype
International audiencePretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: the transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/ml) at day 10. Our results indicate that the incidence of biopsy proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Parients death, cancer, cardiovascular events and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes
Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD
Introduction: In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods: We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results: Patients' median age was 68 (interquartile range [IQR], 59â76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53â6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18â7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19â1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14â1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion: In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment