Effets non osseux de la vitamine D

Actuellement, la vitamine D doit être considérée comme une prohormone dont les effets dépassent la prévention du rachitisme/ostéomalacie. De nombreux tissus sont capables de convertir localement la 25-hydroxyvitamine D en calcitriol qui aura alors des actions auto/paracrines sur la prolifération et la différenciation cellulaires, l’apoptose, les sécrétions d’insuline et de rénine, la production d’interleukines et la bactéricidie. Des données épidémiologiques et expérimentales sont en faveur d’un rôle protecteur de la vitamine D contre les cancers, le diabète de type 2, les maladies cardiovasculaires, auto-immunes, infectieuses, rénales et le déficit musculaire. Quelques études d’intervention confirment certains de ces effets

Implication du stress du réticulum endoplasmique en transplantation d’organe solide

Le stress du réticulum endoplasmique (RE) est produit par l’accumulation de protéines mal conformées dans le RE et conduit à l’activation d’une réponse adaptative, la réponse UPR (unfolded protein response). Le stress du RE est impliqué dans la pathogénie de nombreuses pathologies telles que la maladie d’Alzheimer, l’athérosclérose, les diabètes de types 1 et 2 ou certaines maladies inflammatoires du tube digestif. Des données expérimentales récentes suggèrent son implication en transplantation d’organe solide. L’objet de cette revue est de synthétiser les données sur les mécanismes moléculaires du stress du RE et les conséquences de celui-ci en pathologie, et plus particulièrement à partir de plusieurs modèles de transplantation d’organes solides et de lésions tissulaires dans lesquels le stress du RE peut être impliqué. Nous discutons aussi les implications possibles du stress du RE, au-delà de la simple réponse adaptative et de la régulation de la mort cellulaire, sur les modifications des propriétés fonctionnelles et les changements phénotypiques. La modulation de la réponse UPR au cours du stress du RE en transplantation d’organe solide pourrait constituer une cible thérapeutique prometteuse. La mise en évidence de marqueurs du stress du RE tels que BiP/GRP78 ou CHOP dans les biopsies de greffon pourrait permettre la détection précoce d’un processus pathologique en cours avant que les lésions histologiques ne soient définitivement établies. L’autre enjeu serait de trouver une stratégie pour bloquer la mort cellulaire causée par le stress du RE, ce qui fournit un champ d’investigation passionnant pour de futurs traitements protecteurs

Utilisation du fer en néphrologie : enquête sur les pratiques des néphrologues 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) ≥15 mL min−1/1.73 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 min−1/1.73 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 &lt; 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 système rénineangiotensine- aldostérone, qui joue un rôle important dans le développement des lésions glomérulaires et tubulo-interstitielles et dans l’apparition de la protéinurie, mais aussi l’activation de la voie NF-kB qui est connue pour favoriser la maladie rénale chronique en stimulant l’inflammation et la fibrogenèse. Les effets pléiotropes de la vitamine D sont également très intéressants pour le patient insuffisant rénal (diminution de la mortalité, de la protéinurie et effets anti-inflammatoires). De plus, l’administration de vitamine D native (cholécalciférol ou ergocalciférol) diminue les concentrations sériques de parathormone. La supplémentation en vitamine D native chez l’insuffisant rénal n’entraîne pas de toxicité ni d’augmentation du risque de calcification vasculaire malgré les effets hypercalcémiants et hyperphosphorémiants de cette molécule sous sa forme active. La vitamine D per se (c’est-à-dire sans apports calciques excessifs), aux doses habituellement utilisées en clinique, n’est pas associée à une augmentation du risque de lithiase urinaire. Dans le domaine de la transplantation rénale, les études expérimentales montrent un rôle protecteur des analogues de la vitamine D contre le rejet aigu, mais les études cliniques restent à 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], 59–76) 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], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) 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, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). 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