Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease

Background: Uremic solute concentration increases as Glomerular Filtration Rate (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR) and the concentrations of several small water-soluble and protein-bound uremic solutes (MW500Da). Materials and Methods: In 95 CKD-patients (CKD-stage 2-5 not on dialysis), associations between different eGFR-formulae (creatinine, CystatinC-based or both) and the natural logarithm of the concentration of several LMWP's were analyzed: i.e. parathyroid hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), leptin, retinol binding protein (RbP), immunoglobin light chains kappa and lambda (Ig-kappa and Ig-lambda), beta-2-microglobulin (beta M-2), myoglobin and fibroblast growth factor-23 (FGF-23)). Results: The regression coefficients (R-2) between eGFR, based on the CKD-EPI-Crea-CystC-formula as reference, and the examined LMWP's could be divided into three groups. Most of the LMWP's associated weakly (R-2 0.7). Almost identical R-2-values were found per LMWP for all eGFR-formulae, with exception of CystC and beta M-2 which showed weaker associations with creatinine-based than with CystC-based eGFR. Conclusion: The association between eGFR and the concentration of several LMWP's is inconsistent, with in general low R-2-values. Thus, the use of eGFR to evaluate kidney function does not reflect the concentration of several LMWP's with proven toxic impact in CKD

Cursive Eye-Writing With Smooth-Pursuit Eye-Movement Is Possible in Subjects With Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing a progressive motor weakness of all voluntary muscles, whose progression challenges communication modalities such as handwriting or speech. The current study investigated whether ALS subjects can use Eye-On-Line (EOL), a novel eye-operated communication device allowing, after training, to voluntarily control smooth-pursuit eye-movements (SPEM) so as to eye-write in cursive. To that aim, ALS participants (n = 12) with preserved eye-movements but impaired handwriting were trained during six on-site visits. The primary outcome of the study was the recognition of eye-written digits (0–9) from ALS and healthy control subjects by naïve “readers.” Changes in oculomotor performance and the safety of EOL were also evaluated. At the end of the program, 69.4% of the eye-written digits from 11 ALS subjects were recognized by naïve readers, similar to the 67.3% found for eye-written digits from controls participants, with however, large inter-individual differences in both groups of “writers.” Training with EOL was associated with a transient fatigue leading one ALS subject to drop out the study at the fifth visit. Otherwise, itching eyes was the most common adverse event (3 subjects). This study shows that, despite the impact of ALS on the motor system, most ALS participants could improve their mastering of eye-movements, so as to produce recognizable eye-written digits, although the eye-traces sometimes needed smoothing to ease digit legibility from both ALS subjects and control participants. The capability to endogenously and voluntarily generate eye-traces using EOL brings a novel way to communicate for disabled individuals, allowing creative personal and emotional expression

Association between metformin use and below-the-knee arterial calcification score in type 2 diabetic patients.

BACKGROUND Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk. METHODS The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease. Below-the-knee calcification scores were assessed by computed tomography and supplemented by colour duplex ultrasonography. Data on anti-diabetic drugs were carefully collected from the patients' medical records and during patient interviews. Biochemical and clinical data were studied as potential confounding factors. RESULTS Metformin-treated patients had a significantly lower calcification score than metformin-free patients (mean ± standard deviation: 2033 ± 4514 and 4684 ± 9291, respectively; p = 0.01). A univariate analysis showed that metformin was associated with a significantly lower prevalence of severe below-the-knee arterial calcification (p = 0.02). VC was not significantly associated with the use of other antidiabetic drugs, including sulfonylureas, insulin, gliptin, and glucagon like peptide-1 analogues. A multivariate logistic regression analysis indicated that the association between metformin use and calcification score (odds ratio [95% confidence interval] = 0.33 [0.11-0.98]; p = 0.045) was independent of age, gender, tobacco use, renal function, previous cardiovascular disease, diabetes duration, neuropathy, retinopathy, HbA1c levels, and inflammation. CONCLUSIONS In patients with type 2 diabetes, metformin use was independently associated with a lower below-the-knee arterial calcification score. This association may contribute to metformin's well-known vascular protective effect. Further prospective investigations of metformin's potential ability to inhibit VC in patients with and without type 2 diabetes are now needed to confirm these results

N-methyl-2-pyridone-5-carboxamide (2PY)—Major Metabolite of Nicotinamide: An Update on an Old Uremic Toxin

N-methyl-2-pyridone-5-carboxamide (2PY, a major metabolite of nicotinamide, NAM) was recently identified as a uremic toxin. Recent interventional trials using NAM to treat high levels of phosphorus in end-stage renal disease have highlighted new potential uremic toxicities of 2PY. In the context of uremia, the accumulation of 2PY could be harmful—perhaps by inhibiting poly (ADP-ribose) polymerase-1 activity. Here, we review recently published data on 2PY’s metabolism and toxicological profile

Place du pharmacien dans la prévention secondaire de l'accident vasculaire cérébral

L accident vasculaire cérébral (AVC) est la complication aiguë d une maladie vasculaire, due à un arrêt de vascularisation sanguine dans un territoire cérébral ou à une rupture d un vaisseau. Il représente en France la 3ème cause de mortalité et la 1ère cause d invalidité. Les lésions cérébrales entraînent des déficiences variées. Le nombre de nouveaux cas annuels est évalué à 130 000 pour la France, et 35 000 récidives par an chez d anciens malades, d où l importance de mettre en place une prévention secondaire qui a pour objectif d éviter la récidive ultérieure. Les traitements de prévention secondaire sont pourtant mal suivis, malgré leur efficacité vraisemblable sur la fréquence et la gravité des récidives. Notre étude illustre ce problème. Les pharmaciens ont un rôle à jouer dans l éducation pour la santé. Après avoir identifié le projet thérapeutique du malade, le pharmacien évalue le niveau d adhésion du patient, identifie les facteurs de risque personnels, explique et informe sur la pathologie et son traitement, soutien et accompagne le malade. Il est de leur devoir professionnel de veiller au bon usage du médicament, à l observance médicamenteuse, d informer, et de promouvoir la prévention et le dépistage des facteurs de risque cardiovasculaire.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Association between free light chain levels, and disease progression and mortality in chronic kidney disease

Immunoglobulin free light chains (FLCs) form part of the middle molecule group of uremic toxins. Accumulation of FLCs has been observed in patients with chronic kidney disease (CKD). The aim of the present study was to measure FLC levels in patients at different CKD stages and to assess putative associations between FLC levels on one hand and biochemical/clinical parameters and mortality on the other. One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry assays and assays for FLC kappa () and lambda () and other uremic toxins were performed. Vascular calcification was evaluated using radiological techniques. The enrolled patients were prospectively monitored for mortality. Free light chain and levels were found to be elevated in CKD patients (especially in those on hemodialysis). Furthermore, FLC and levels were positively correlated with inflammation, aortic calcification and the levels of various uremic toxins levels. A multivariate linear regression analysis indicated that FLC and levels were independently associated with CKD stages and 2 microglobulin levels. Elevated FLC and levels appeared to be associated with mortality. However, this association disappeared after adjustment for a propensity score including age, CKD stage and aortic calcification. In conclusion, our results indicate that FLC and levels are elevated in CKD patients and are associated with inflammation, vascular calcification and levels of other uremic toxins. The observed link between elevated FLC levels and mortality appears to depend on other well-known factors

Bon usage des anticoagulants oraux et conformité de l’analyse pharmaceutique : audit sur les prescriptions hospitalières

Introduction : Les anticoagulants oraux font partie des classes médicamenteuses responsables du plus grand nombre d’évènements iatrogènes dans le monde et notamment en France.  Objectifs : Vérifier la conformité de la prescription des antivitamines K (acénocoumarol, fluindione, warfarine) et des anticoagulants oraux directs (apixaban, dabigatran, rivaroxaban), ainsi que la conformité de l’analyse pharmaceutique associée avec les recommandations européennes et françaises.  Description de la problématique : Au sein d’un établissement hospitalo-universitaire de 1673 lits, un audit prospectif a été mené le 15 juillet 2019. Les dossiers des patients hospitalisés recevant un anticoagulant oral ont été consultés afin d’évaluer les informations relatives à leur prescription (âge, poids, fonction rénale, rapport international normalisé, indication…) et, ainsi, de vérifier leur bon usage.  Résolution de la problématique : Parmi les 123 patients traités par un anticoagulant oral (moyenne d’âge 81,9 ± 11,5 ans), 87 % (107) recevaient un anticoagulant oral direct. La molécule choisie était adaptée à l’indication dans 98 % (121) des cas; la prescription a été évaluée conforme dans 71 % (86) des cas. La majorité des non-conformités étaient dues à un rapport international normalisé hors de la cible thérapeutique chez 75 % (12) des patients sous antivitamines K. Le taux de prescriptions analysées par les pharmaciens était de 93 % (114); cette analyse a été considérée comme conforme dans 69 % (84) des cas.  Conclusion : À travers cette étude, des points de non-conformité ont pu être mis en avant sur l’analyse pharmaceutique. Ce travail a permis de sécuriser cette étape du circuit par la création de nouvelles règles d’alerte dans notre système informatique d’aide à l’analyse des prescriptions.  Abstract  Introduction: Oral anticoagulants are among the classes of drugs responsible for the largest number of iatrogenic events in the world, and particularly in France.  Objectives: To check prescribing compliance for antivitamins K (acenocoumarol, fluindione and warfarin), direct oral anticoagulants (apixaban, dabigatran and rivaroxaban), the compliance and the related pharmaceutical analysis with European and French recommendations.  Problem description: A prospective audit was conducted at a 1673-bed teaching hospital on July 15, 2019. The charts of the inpatients receiving an oral anticoagulant were consulted for the purpose of examining the information pertaining to their prescription (age, weight, renal function, international normalized ratio, indication, etc.) to check that it was being used properly.  Problem resolution: Of the 123 patients being treated with an oral anticoagulant (mean age: 81.9 ± 11.5 years), 87% (107) were receiving a direct oral anticoagulant. The drug chosen was appropriate for the indication in 98% (121) of the cases, and the prescription was deemed compliant in 71% (86) of the cases. Most of the instances of noncompliance were due to an international normalized ratio outside the therapeutic target in 75% (12) of the patients taking antivitamins K. The proportion of prescriptions analyzed by the pharmacists was 93% (114), and the analysis was considered compliant in 69% (84) of the cases.  Conclusion: In this study, instances of noncompliance were identified in the pharmaceutical analysis. This work enabled us to make this step of the circuit safer by creating new alert rules in our computer system for prescription analysis.

Le jeu pathologique et les médicaments dopaminergiques

Résumé Objectifs : Présenter le jeu pathologique (JP), ef­fet indésirable peu connu des agonistes dopaminer­giques, au travers de quatre notifications rapportées au Centre régional de pharmacovigilance d’Amiens (France). Discussion : Les premiers cas de jeu pathologique sous agoniste dopaminergique datent de 2000 et ont été rapportés dans le contexte d’une maladie de Par­kinson. Depuis, d’autres cas sont décrits avec ces médicaments utilisés à plus faibles posologies et dans un autre contexte. Le jeu pathologique corres­pond à une dépendance qui apparaît de façon insi­dieuse et peut passer inaperçue. L’existence d’anté­cédents neuropsychiatriques ou de comportements compulsifs semble favoriser la survenue de cet effet indésirable. Les conséquences peuvent être extrê­mement négatives sur la vie des patients. La détec­tion précoce de cette pathologie est primordiale d’autant que la diminution, voire l’arrêt du traite­ment, suffit souvent à faire disparaître la symptoma­tologie. Les médicaments les plus incriminés sont les agonistes dopaminergiques non ergotés (ropini­role et pramipexole) en raison de leur forte affinité pour les récepteurs D3 de la dopamine. Conclusion : La détection d’un jeu pathologique implique une reconsidération de la stratégie théra­peutique dans les plus brefs délais. La gravité poten­tielle de ce type d’atteinte doit inciter les médecins à informer les patients et leur entourage sur la possibi­lité de survenue de cet effet indésirable. Nous insis­tons sur l’importance du suivi postautorisation de mise sur le marché qui permet la mise en évidence de nouveaux signaux non observés au préalable lors des essais cliniques. Abstract Purpose: To discuss pathological gambling (PG), a little known side effect of dopamine agonists, by means of four adverse reaction reports to the Centre régional de pharmacovigilance d’Amiens (France). Discussion: The first cases of pathological gam­bling while under treatment with a dopamine ago­nist were reported in 2000, in the context of Parkin­son’s disease. Subsequently other cases have been described with these medications but at lower doses and in another context. Pathological gambling is a dependence that can appear insidiously and can go unnoticed. A history of neuropsychiatric disorder or of compulsive behaviour seems to favour the deve­lopment of this side effect. Pathological gambling can have extremely negative consequences on pa­tient’s lives. Early detection is crucial, and de­creasing or even discontinuing the treatment should be enough to cause for symptoms to disappear. The most incriminating medications are non-ergot dopa­mine agonists (ropinirole and pramipexole) because of their strong affinity for dopamine D3 receptors. Conclusion: The detection of pathological gam­bling in a patient implies that a clinical approach must quickly be reevaluated. The potential severity of this problem must prompt physicians to inform patients and their families of the possibility of this side effect. We insist on the importance of post-mar­keting surveillance, allowing the detection of signals that were not observed during clinical trials. Key words: Pathological gambling; dopamine agonists; dependence; impulse control disorder; pharmacovigilance