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BackgroundThe risk of fragility fractures is high in kidney transplant recipients, and steroids are reportedly a major cause. Other drugs known to induce fragility fractures have been studied in the general population but not in kidney transplant recipients. Here, we investigated the association between exposure over time to drugs that can injure bone (namely vitamin K antagonists, insulin, loop diuretics, proton pump inhibitors, opioids, selective serotonin reuptake inhibitors, antiepileptics and benzodiazepines) and incident fractures and changes over time in T-scores in this population.MethodsA total of 613 consecutive kidney transplant recipients were included between 2006 and 2019. Drug exposures and incident fractures during the study period were comprehensively documented, and dual-energy X-ray absorptiometry was performed regularly. The data were analyzed using Cox proportional hazards models with time-dependent covariates and linear mixed models.ResultsIncident fractures occurred in 63 patients, giving a fracture incidence of 16.9 per 1000 person-years. Exposures to loop diuretics [hazard ratio (95% confidence interval) 2.11 (1.17–3.79)] and opioids [5.94 (2.14–16.52)] were associated with incident fractures. Exposure to loop diuretics was associated with a decrease over time in the T-score for the lumbar spine (P = .022) and for the wrist (P = .028).ConclusionsThis study suggests that the exposure to loop diuretics and opioids increases the risk of fracture in kidney transplant recipients.

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Background Medication regimen complexity (MRC) has not been characterized in detail in patients with end-stage renal disease (ESRD). The objective of the present study was to quantify changes over time in the prescription drug burden and MRC in patients with ESRD (before transplantation, on discharge after kidney transplantation [M0], and 4 months [M4] and 12 months [M12] afterward). Methods We retrospectively studied adult patients having undergone kidney transplantation. The number and types of drug prescribed, the pill burden, and the MRC index (MRCI) at 4 different time points (before transplantation, M0, M4, and M12) were extracted from the patients’ medical records. MRCI was calculated by adding each drug score (calculated according to its formulation, dosing frequency, and additional instructions concerning administration). Hence, the MRCI took account of all prescription drugs. A logistic regression model was used to identify factors associated with an elevated MRCI at M12. Results The median (interquartile range) age of the 354 study participants was 52 years (42–62). Respectively 21%, 42%, 53%, and 38% of the patients were taking 10 or more drugs before transplantation and at M0, M4, and M12. At M12, the 3 most frequently prescribed drug classes were immunosuppressants, cardiovascular system drugs, and drugs acting on the alimentary tract and metabolism. The pill burden and MRCI before transplantation were significantly lower (P Conclusion In kidney transplant recipients, the drug burden and MRCI were greater at all time points after transplantation than before transplantation. The impact of the drug burden and MRC on medication adherence and clinical outcomes in these patients requires further evaluation.

Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR.

The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: r =0.40 versus 0.30; WC: r =0.40 versus 0.30, both P ID and II ACE genotypes in both sexes ( P ACE genotype only in women ( P =0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15–2.10], P =0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09–3.20], P =0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.

Background and Aims The use of oral antithrombotics in patients with chronic kidney disease (CKD) is challenging because of altered pharmacodynamics/pharmacokinetics. Patients prescribed oral anticoagulant are at high risk of bleeding, and possibly also acute kidney injury (AKI) and progression to kidney failure. We assessed bleeding, AKI, and kidney failure risks associated with oral anticoagulant and/or antiplatelet agent prescription in patients with moderate-to-advanced CKD. Method CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at inclusion. Drug prescriptions and their duration were collected prospectively. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HR) for bleeding (identified through hospitalizations), AKI (as defined according to KDIGO 2012), and kidney failure. Prescriptions of oral antithrombotics were treated as a time dependent variable and models were adjusted for baseline comorbidities, laboratory data, and other medications. Results At baseline, 339 (11%) patients (65% men; median age 69 [interquartile range (IQR), 60-76] years; median eGFR 32 [IQR, 23-41] were prescribed oral anticoagulants only, 1095 (36%) antiplatelet only, and 101 (3%) both anticoagulant and antiplatelet. Over a median follow-up of 3 years (IQR, 2.8-3.1), 152 patients experienced a bleeding event requiring hospital visit/stay (crude incidence rate (IR): 1.9% person-years [95%CI,1.6-2.2]), 414 patients experienced AKI (crude IR: 5.4 % person-years [4.9-5.9]), and 270 experienced kidney failure (crude IR: 3.4 % person-years [3.0-3.8]). A significant interaction was found between oral antithrombotics and eGFR (interaction p=0.03). The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.58 [0.30; 1.11], 2.62 [1.39; 4.93], and 5.76 [2.85; 11.66] in patients with a baseline eGFR < 30 mL/min/1.73m2. In patients with baseline eGFR ≥ 30 mL/min/1.73m2, the adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants .......only, and antiplatelet + oral anticoagulant were respectively 0.98 [0.48; 1.98], 1.91 [0.87; 4.20], and 1.54 [0.46; 5.12] (Figure 1A). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.91[1.48; 2.46]) but not the prescription of antiplatelets (1.24[0.98; 1.56], Figure 1B). No significant interactions were found between oral anticoagulants and eGFR or antiplatelet agents. Kidney failure was not associated with the prescription of oral antithrombotics of any type (Figure 1C). No significant interactions were found with eGFR and antiplatelet agents. Conclusion This study confirms the risk of AKI in CKD patients prescribed oral anticoagulants. It also highlights the potential aggravating effect of combining anticoagulants and antiplatelet on the risk of bleeding in this population.

Background and Aims Prescription of anticoagulants in patients with chronic kidney disease (CKD) is challenging, since these patients are at high risk of thromboembolic episodes, but are also prone to bleeding events. Based on a number of pivotal trials, four direct oral anticoagulants (DOACs) have been approved for use in non-valvular atrial fibrillation (AF) since 2010. These DOACs have now supplanted vitamin K antagonists (VKAs) as first-line treatment in non-CKD patients. Following post-hoc analyses of randomized clinical trials of DOACs in CKD patients performed between 2011 and 2016, a 2018 Kidney Disease Improving Global Outcomes Controversies Conference stated that although there is not enough evidence to recommend DOACs in patients with advanced CKD, these medications are safer than VKAs and not inferior for stroke preventing in patients with AF and an estimated glomerular filtration rate (eGFR) between 30 and 50 ml/min/1.73 m2. Here, in a study of stage 3 to 5 CKD patients, we sought to describe multinational prescription patterns for oral anticoagulants in general and for VKAs vs. DOACs in particular. Method We analyzed data from the international CKD Outcomes and Practice Patterns Study (CKDopps) of non-dialysis CKD patients ≥ 18 years of age with an eGFR Results Of the 8154 patients enrolled, 7092 had drug prescriptions data available at baseline, and 1080 (15%) of these had at least one prescription of an oral anticoagulant. At baseline, VKAs were the most frequently prescribed oral anticoagulants (n=984, 91%), and only 97 of the 1080 patients (9%) were on DOACs (91 on a direct factor Xa inhibitor and 6 on a direct thrombin inhibitor). This low DOAC prescription rate was observed in France, the USA, Brazil and Germany. There was an upward trend in DOAC prescription (relative to VKAs) over the course of the study. Over a median [interquartile range] follow-up period of 3 years [1.5-4.5], 287 incident oral anticoagulant prescriptions were reported, 177 started on VKAs and 110 started on DOACs. Among the patients receiving a VKA at baseline, only 44 switched to a DOAC. Conclusion In an international sample of non-dialysis CKD patients (eGFR

The affiliation details for Geltrude Mingrone are corrected below.

International audience; Chronic kidney disease (CKD) is a highly prevalent condition and is associated with a high comorbidity burden, polymedication, and a high mortality rate. A number of conventional and nonconventional risk factors for comorbidities and mortality in CKD have been identified. Among the nonconventional risk factors, uremic toxins are valuable therapeutic targets. The fact that some uremic toxins are gut-derived suggests that intestinal chelators might have a therapeutic effect. The phosphate binders used to prevent hyperphosphatemia in hemodialysis patients act by complexing inorganic phosphate in the gastrointestinal tract but might conceivably have a nonspecific action on gut-derived uremic toxins. Since phosphorous is a major nutrient for the survival and reproduction of bacteria, changes in its intestinal concentration may impact the gut microbiota's activity and composition. Furthermore, AST-120 is an orally administered activated charcoal adsorbent that is widely used in Asian countries to specifically decrease uremic toxin levels. In this narrative review, we examine the latest data on the use of oral nonspecific and specific intestinal chelators to reduce levels of gut-derived uremic toxins.

Background: Uremic toxins have emerged as potential mediators of morbidity and mortality in patients with chronic kidney disease (CKD). Indole-3-acetic acid (IAA, a tryptophan-derived uremic toxin) might be a useful biomarker in patients with CKD. The objectives of the present study were to (i) describe IAA concentrations in a cohort of non-transplanted patients with CKD and a cohort of transplanted patients with CKD, and (ii) investigate the possible relationship between IAA levels and adverse outcomes in the two cohorts. Methods: Levels of free and total IAA were assayed in the two prospective CKD cohorts (140 non-transplanted patients and 311 transplanted patients). Cox multivariate analyses were used to evaluate the association between IAA levels and outcomes (mortality, cardiovascular events, and graft loss). Results: In the non-transplanted CKD cohort, free and total IAA increased progressively with the CKD stage. In the transplanted CKD cohort, free and total IAA levels were elevated at the time of transplantation but had fallen substantially at one-month post-transplantation. Indole acetic acid concentrations were lower in transplanted patients than non-dialysis non-transplanted patients matched for estimated glomerular filtration rate (eGFR), age, and sex. After adjustment for multiple confounders, the free IAA level predicted overall mortality and cardiovascular events in the non-transplanted CKD cohort (hazard ratio [95% confidence interval]: 2.5 [1.2&ndash, 5.1] and 2.5 [1.3&ndash, 4.8], respectively). In the transplanted CKD cohort, however, no associations were found between free or total IAA on one hand, and mortality, CV event, or graft survival on the other. Conclusion: We demonstrated that levels of IAA increase with the CKD stage, and fall substantially, even normalizing, after kidney transplantation. Free IAA appears to be a valuable outcome-associated biomarker in non-transplanted patients, but&mdash, at least in our study setting&mdash, not in transplanted patients.

International audience; BACKGROUND AND OBJECTIVES: Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR\textless60 ml/min per 1.73 m(2), with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology. RESULTS: Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m(2), and 45% had eGFR\textless30 ml/min per 1.73 m(2). Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR\textless30 versus ≥30 ml/min per 1.73 m(2) (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4). CONCLUSIONS: Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.

International audience; AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m(2) at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

Aims Drug prescription is difficult to manage in patients with chronic kidney disease (CKD). We assessed the prevalence and determinants of inappropriate drug prescriptions (whether contraindications or inappropriately high doses) with regard to kidney function in patients with CKD under nephrology care. We also assessed the impact of the equation used to estimate GFR on the prevalence estimates. Methods Results The CKD-REIN cohort includes 3033 outpatients with CKD (eGFR between 15 and 60 ml min(-1) 1.73 m(-2)). We examined the daily doses of pharmacological agents prescribed at study entry. Inappropriate prescription was defined as the reported prescription of either a contraindicated drug or an indicated drug at an inappropriately high dose level with regard to the patient's GFR, as estimated with the CKD-EPI equation, the de-indexed CKD-EPI equation, or the Cockcroft-Gault (CG) equation. Multivariate logistic regression was used to assess the determinants of inappropriate prescription risk. At baseline, patients' median [interquartile range] number of drugs prescribed per patient was 8 [5-10]. Half of the patients had been prescribed at least one inappropriate drug. Anti-gout, cardiovascular agents and antidiabetic agents accounted for most of the inappropriate prescriptions. The percentage of inappropriate prescriptions varied from one GFR equation to another: 52% when using the CKD-EPI equation, 47% when using the de-indexed CKD-EPI equation and 41% with the CG equation. A multiple logistic regression analysis showed significantly higher odds ratios [95% confidence interval] for inappropriate prescriptions in male patients (1.28 [1.07; 1.53]), patients with diabetes (1.34 [1.06; 1.70]), those with a high BMI (1.58 [1.25; 1.99]), and those with a low GFR (10.2 [6.02; 17.3]). The risk of having at least one inappropriate prescription increased with the number of drugs per patient (P for trend \textless 0.0001) and therefore the odds ratio was 5.88 [4.17; 8.28] for those who received at least 11 prescribed medications compared to those who received fewer than 5. Conclusion Appendix Our results emphasize the complexity of drug management for CKD patients, for whom inappropriate prescription appears to be common.

Introduction La maladie renale chronique (MRC) moderee a severe augmente la susceptibilite des patients a la survenue d’effets indesirables medicamenteux (EIM). L’objectif de ce travail est de decrire les caracteristiques des EIM, rapportes ou non par les patients. Description CKD-REIN inclut 3033 patients atteints de MRC avec un debit de filtration glomerulaire estime ≤ 60 mL/min/1,73 m2. Methodes Les EIM etaient recueillis annuellement dans le dossier medical et par interview des patients avec la question : « Avez-vous eu un effet indesirable medicamenteux ? » et « Si oui, lequel ? ». Tous les EIM ont ete expertises et codes par des pharmaciens. L’imputabilite et l’evitabilite des EIM graves ont ete evaluees en centre regional de pharmacovigilance. Resultats Sur un suivi median de 3 ans [2,8–3,1], 1173 EIM (dont 316 graves) sont survenus chez 756 patients (taux d’incidence : EIM, 14,2 [13,4–15,0] pour 100 personne-annees (PA) ; EIM graves, 3,8 [3,4–4,3] pour 100 PA). La majorite des EIM a ete rapportee dans le dossier medical seulement (66 %), 177 (15 %) ont ete rapportes dans le dossier medical et par le patient, et 224 (19 %) ont ete rapportes par le patient uniquement. Alors que les affections du rein et des voies urinaires (67 % d’insuffisances renales aigues) et gastro-intestinales etaient les plus frequentes, les affections musculosquelettiques et du tissu conjonctif etaient les plus declarees par les patients ( Fig. 1 ). Parmi les 316 EIM graves, 5 (2 %) etaient declares uniquement par le patient, 21 (7 %) mentionnes par le patient et dans le dossier medical, et 290 (92 %) retrouves uniquement dans le dossier medical. Un quart des EIM graves (n = 83) etaient consideres evitables ou potentiellement evitables, parmi lesquels 14 etaient dus a un non-respect des recommandations ou une negligence de la part du patient. Conclusion Les patients identifient tres peu les EIM notamment les plus graves. Informer les patients grâce a des seances d’education therapeutique pourrait permettre d’en eviter certains.

Background For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat. Methods We carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs). Results Among 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs. Conclusions Acute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

International audience

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR)

Introduction On dispose de peu de donnees sur le parcours des patients atteints de polykystose renale familiale (PKR) pris en charge en dialyse peritoneale (DP). Description Nous avons, a l’aide du registre de dialyse a domicile de langue francaise, revu les dossiers des 28 patients atteints de PKR pris en charge en DP en premiere intention dans notre centre depuis 1997. Methodes Analyse retrospective du devenir des patients PKR. Resultats Il s’agit de 13 hommes et 15 femmes, âges en moyenne de 54 ans (extremes 33–75 ans). Aucun patient n’est diabetique. Neuf patients n’ont aucune comorbidite, trois sont porteurs d’une cardiopathie severe, trois ont un IMC > 30. Le Charlson est > 4 chez cinq patients. La majorite des patients (23 patients) est traitee par dialyse peritoneale automatisee (DPA) nocturne, un seul patient est non autonome. Le temps de suivi pour l’ensemble des patients est de 811 mois, soit 29 mois en moyenne par patient. Un seul patient a necessite une nephrectomie pour preparation a la transplantation renale. Onze patients ont presente une infection peritoneale. Le nombre total de peritonite est de 22. L’incidence des peritonites infectieuses est d’un episode patient tous les 37 mois. Dans neuf cas il s’agissait d’un bacille gram negatif. L’infection peritoneale a conduit a la perte brutale de la DP dans un cas et au deces d’un patient dans un autre cas. Quinze patients (54 %) ont beneficie d’une transplantation renale. Six patients (21 %) ont ete transferes en hemodialyse (moyenne de 41 mois). Quatre patients sont decedes dont deux brutalement a domicile. Trois patients sont actuellement traites par DP. Conclusion Ce travail confirme que la DP, en particulier la DPA nocturne, est une bonne option de traitement (survies patient et technique, incidence des peritonites) dans la polykystose renale, en particulier pour ceux en attente de transplantation renale.

Introduction et but de l’etude Le syndrome metabolique est associe a une faible richesse bacterienne du microbiote intestinal. Il a ete demontre qu’une intervention alimentaire de courte duree permettait de retablir partiellement cette richesse du microbiote intestinal et ameliorait en parallele le profil cardiometabolique (CM). Notre objectif est de determiner comment une intervention nutritionnelle simple, utilisant un produit de consommation courante le pain pourrait par l’augmentation de l’apport en fibres (quantite et diversite) moduler le microbiote intestinal, le profil lipidique et l’insulino-sensibilite chez les sujets a risque CM. Materiel et methodes Pour cette etude en double aveugle randomisee en cross-over, 39 sujets a risque CM (obesite abdominale) et presentant une faible consommation de fibres ( Resultats et analyse statistique Les sujets a risque CM presentaient a l’inclusion, une richesse bacterienne plus faible en comparaison a une cohorte de reference de sujets sains. L’intervention avec le pain enrichi en fibres n’a pas modifie la richesse en genes du microbiote intestinal mais l’abondance relative de certaines especes a ete modifiee: diminution significative de Bacteroides vulgatus (p Conclusion La consommation pendant deux mois d’un pain enrichi en un melange de fibres selectionnes a modifie l’abondance relative de certaines especes bacteriennes intestinales, en parallele d’une amelioration significative du profil lipidique et de la sensibilite a l’insuline. L’augmentation de l’apport en fibres en termes de quantite et de diversite sous forme de pain specifique pourrait etre utilise pour ameliorer le profil CM.

In the original publication of this article, the members of the FORTA group were provided in such a way that they could not be indexed as collaborators on PubMed. The article should have included an Acknowledgement section as shown below.

Duplex ultrasonography screening for renal artery stenosis has been the object of guidelines published by four societies designed to optimize the cost-effectiveness of the examination.To determine how well guideline indications for ultrasonography matched with requests and results in our university hospital; to determine whether compliance with guidelines was predictive of renal artery stenosis; to identify guidelines predictive of presence of stenosis; and to determine whether other predictive factors can be recognized.Requests and results of 450 Duplex ultrasonography examinations of the renal arteries performed from January 1st 2014 to December 31st 2015 were compared with published guidelines.At least one guideline indication was identified for 212 of the 450 examinations performed (47.1%). Among these examinations, renal artery stenosis≥70% was identified in 18 patients (8.0%). No case of stenosis was identified during examinations performed outside guideline indications. Factors predictive of stenosis were: compliance with guidelines (OR=21.86 [2.88; 165.8]). Predictive guidelines were: resistant hypertension in spite of appropriate treatment (OR=3.85, [1.44; 10.33], P=0.011), accelerated hypertension (OR=7.30, [1.40; 37.99], P=0.049), sudden unexplained pulmonary edema (OR=7.30, [1.40; 37.99], P=0.049), unexplained renal insufficiency (OR=3.58, [1.37; 9.37], P=0.011), unexplained renal hypotrophy (OR=16.69, [4.38; 63.69], P0.001), renal asymmetry (OR=4.32, [1.45; 12.85], P0.016). No other factor was predictive of renal stenosis. These examinations had therapeutic consequences in only 50% of patients.This study confirms the relevance of published guidelines. The diagnostic-effectiveness of Duplex ultrasonography examinations to search for renal artery stenosis depends upon compliance with these guidelines.

Resume Introduction La duree de traitement des dysplasies developpementales de la hanche chez le nouveau-ne varie selon le credit accorde a l’influence du maintien du harnais de Pavlik sur l’evolution de la dysplasie acetabulaire. Une premiere theorie soutient qu’apres reduction, la prolongation de plusieurs mois du port du harnais participe a la correction de la dysplasie acetabulaire. La deuxieme, celle de la luxation dysplasiante, s’appuie sur les capacites de correction spontanee de la dysplasie acetabulaire sur hanche centree. Ce travail vise a evaluer cette deuxieme theorie sur des hanches traitees de facon precoce et courte par harnais de Pavlik. Hypothese Les dysplasies acetabulaires associees aux instabilites neonatales de hanche se corrigent spontanement, a condition que la hanche soit reduite et stabilisee tres precocement. La duree de port du harnais de Pavlik peut alors etre considerablement reduite. Patients et methodes La hanche etait consideree comme instable lorsque celle-ci etait luxee, reductible ou tres facilement luxable avec perception d’un « ressaut mou » de luxation, ne permettant pas de s’assurer de la position naturelle luxee ou reduite de la hanche. L’echographie etait statique et dynamique. Une instabilite echographique (distance epiphyse-fosse acetabulaire > 5 mm, et couverture inferieure a 50 %) devait inciter a renouveler l’examen clinique et a proposer un traitement. Quarante-deux hanches pathologiques chez 30 patients ont ete revues a 6,7 ans (5–14) de recul. L’âge moyen lors du traitement etait de 5 jours (1–15) et sa duree moyenne de 34 jours (15–75). Resultats L’angle acetabulaire moyen etait de 20° (12–30), l’angle de Wiberg de 30° (22–35°). Un emoussement de l’angle lateral du toit osseux etait retrouve sur 8 hanches au plus long recul. Une reluxation a 5 mois etait observee apres obtention d’une stabilite clinique, mais pas echographique, a 21 jours. Le score de Severin etait de l a chez tous les patients. Discussion Bien que la theorie de la luxation dysplasiante et de la dysplasie luxante s’affrontent, le traitement precoce fait l’unanimite, meme si sa duree varie. Certains auteurs confirment le facteur etiologique familial et vont dans le sens d’une evolution genetiquement programmee de la forme de l’acetabulum sur hanche centree, mais d’autres prolongent systematiquement le port du harnais pour une duree de 2 mois et plus, justifiee par le risque de recidive de la luxation et par la decharge mecanique supposee favorable a la disparition de la dysplasie. Dans cette etude, la duree moyenne de traitement etait de 34 jours, l’objectif unique etant de traiter l’instabilite. La hanche etait donc reduite et maintenue en place le temps necessaire a la retraction capsulo-ligamentaire permettant sa stabilisation. La correction de la dysplasie acetabulaire etait alors spontanee et n’etait pas influencee par la prolongation du traitement. Conclusion La mise en place tres precoce du harnais de Pavlik repond a un choix de reduction et de stabilisation rapide de la hanche, permettant de profiter au maximum du potentiel spontane de remodelage de l’acetabulum. Niveau d’evidence 4.

Background The recommended treatment duration in neonates with developmental dysplasia of the hip (DDH) varies depending on whether prolonged Pavlik harness therapy is believed to favourably affect the course of the acetabular dysplasia. According to one theory, several months of additional Pavlik harness therapy after achieving hip reduction contributes to correct the acetabular dysplasia. Another theory holds that hip dislocation induces the acetabular dysplasia, which corrects spontaneously once the femoral head is properly seated in the acetabulum. Here, we evaluated this second theory by studying outcomes after early brief Pavlik harness therapy. Hypothesis Acetabular dysplasia associated with neonatal hip instability undergoes self-correction provided stable hip reduction is achieved very early after birth. Therefore, the duration of Pavlik harness therapy can be substantially shortened. Materials and methods We defined hip instability as either reducible hip dislocation or a very easily dislocatable hip with a soft clunk precluding determination of spontaneous hip position as dislocated or reduced. Static and dynamic ultrasound scans were obtained. Patients with ultrasonographic instability (pubo-femoral distance > 5 mm with less than 50% of coverage) underwent a second physical examination and received treatment. We re-evaluated 42 abnormal hips in 30 patients after a mean follow-up of 6.7 years (range, 5–14 years). Mean age at treatment initiation was 5 days (range, 1–15 days) and mean treatment duration was 34 days (range, 15–75 days). Results Mean acetabular angle was 20° (range, 12°–30°) and mean Wiberg's lateral centre-edge angle was 30° (range, 22°–35°). Blunting of the lateral angle of the bony roof was noted in 8 hips at last follow-up. In 1 patient whose hip was stable clinically but unstable by ultrasonography at 21 days of age, recurrent dislocation occurred at 5 months of age. The Severin class was 1a in all patients. Discussion Despite continuing controversy about whether hip dislocation induces dysplasia or vice versa, the need for early treatment is universally recognised. The optimal treatment duration, however, remains debated. Proponents of the familial determinism of DDH consider that acetabular shaping is genetically programmed when the femoral head is centred in the acetabular socket. Others advocate routine prolongation of Pavlik harness therapy for 2 months or longer, based on the opinion that this strategy decreases the dislocation recurrence rate and that mechanical hip unloading may promote correction of the dysplasia. Mean treatment duration in our population was 34 days and our sole objective was to treat the instability. The hip was reduced and held in its proper position long enough to allow sufficient capsule and ligament tightening to stabilise the hip. Under these conditions, the acetabular dysplasia underwent self-correction that was not related to treatment duration. Conclusion Very early Pavlik harness therapy to ensure rapid hip reduction and stabilisation optimises the potential of the acetabulum for spontaneous remodelling. Level of evidence Level IV, retrospective study.

Introduction Adapter les doses de medicaments au debit de filtration glomerulaire estime (DFGe) par equation est difficile, notamment chez les personnes obeses. Nous avons evalue la prevalence de prescriptions non adaptees chez des patients atteints de maladie renale chronique (MRC), en estimant le DFG par l’equation CKD-EPI, indexee ou non a la surface corporelle (SC). Patients/Materiels et methodes Dans une cohorte incluant 3033 patients suivis en nephrologie pour une MRC avec un DFGe entre 15 et 60 mL/min/1,73 m2, nous avons examine les doses journalieres de principe actif prescrites dans les 3 mois precedant l’inclusion dans l’etude. Une prescription non adaptee a la fonction renale (fondee sur les recommandations des resumes des caracteristiques des produits) a ete definie comme la prescription declaree d’un medicament contre-indique ou a une dose trop elevee pour le DFGe du patient. Observation/Resultats L’âge median [ecart interquartile] des patients etait de 69 [61–76] ans ; 66 % etaient des hommes, 43 % avaient un diabete et 36 %, un indice de masse corporelle ≥ 30 kg/m2. La SC moyenne etait de 1,90 ± 0,22 m2. Le DFGe moyen etait respectivement de 33 mL/min/1,73 m2 et 36 mL/min, selon que l’equation etait indexee ou non a la SC. Le nombre median de medicaments prescrits etait de 8 [5–10] par jour. La proportion de patients avec au moins une prescription non adaptee au DFGe etait de 52 % avec, et de 47 % sans indexation a la SC. Les hypouricemiants, les antidiabetiques et les medicaments a visee cardiovasculaire etaient les principales classes de medicaments incriminees. Les patients diabetiques avaient avec une SC moyenne de 1,97 ± 0,21 m2 et un DFGe moyen, respectivement, de 33 mL/min/1,73 m2 et 37 mL/min avec et sans indexation a la SC. En consequence, chez les 273 patients sous metformine (seule ou en association), la prescription etait apparemment contre-indiquee chez 53 patients (19 %) avec un DFGe indexe a la SC Discussion/Conclusion La prevalence globale des prescriptions non adaptees a la fonction renale touche pres d’un patient sur deux avec une MRC moderee ou avancee. La prise en compte de la SC pour estimer le DFG induit des variations dans l’evaluation de cette prevalence qui sont d’autant plus importantes que la SC moyenne s’ecarte de la valeur standard de 1,73 m2. Il reste cependant a determiner si la desindexation de l’equation CKD-EPI modifie l’estimation de l’effet de ces prescriptions apparemment non adaptees sur les risques d’evenements iatrogenes, d’hospitalisations et de mortalite.

Discipline Clinique. Introduction et but de l’etude Chez les patients diabetiques de type 2 (DT2), la reduction de la variabilite glycemique et des excursions glycemiques postprandiales pourrait, au-dela du niveau d’HbA1c, etre associee a un meilleur pronostic evolutif. L’alimentation reste la pierre angulaire de la prise en charge du DT2, meme sous traitement hypoglycemiant. Des interventions nutritionnelles regulant la reponse glycemique postprandiale pourraient s’averer pertinentes pour controler la variabilite glycemique de ces patients. En effet, il a ete demontre que la modulation de la digestibilite de l’amidon chez le sujet sain ou intolerant au glucose permet d’obtenir des differences de reponses postprandiales glycemiques et insulinemiques. Le but de cette etude est de determiner si l’augmentation de la teneur de l’alimentation en amidon lentement digestible (SDS) chez des DT2 permet de diminuer les hyperglycemies postprandiales et la variabilite glycemique par rapport a une alimentation classique, a faible teneur en amidon lentement digestible. Materiel et methodes Pour cette etude pilote randomisee en cross-over, huit sujets diabetiques de type 2 (6,5 % ≤ HbA1c ≤ 8,5 %, 22 ≤ IMC ≤ 37 kg/m2, traites par metformine et sitagliptine) ont consomme a 2 reprises pendant une semaine un regime controle contenant des produits amylaces riches ou pauvres en SDS (High-SDS vs Low-SDS, wash-out de 2 semaines). La teneur en SDS de tous les produits amylaces a ete mesuree par la methode SDS. Pendant chaque regime, le profil glycemique a ete evalue pendant 6 jours grâce a un CGMS (Continuous Glucose Monitoring System). Les parametres de variabilite glycemique suivants ont ete calcules : MAGE (Amplitude Moyenne des Excursions Glycemiques), DS (Deviation Standard), CV (Coefficient de Variation), MODD (Moyenne des Differences inter-journalieres), IQR50 (Interquartile 50) et les temps passes dans la cible (TDLC) en periode postprandiale (4 h apres chaque repas). Resultats et analyse statistique La teneur moyenne en SDS des 2 regimes etait significativement differente (Low-SDS 11,4 vs High-SDS 61,4 g/jour ; p Conclusion Une semaine de regime enrichie en SDS chez le patient DT2 permet de diminuer la variabilite du profil glycemique et d’augmenter le temps passe dans une cible glycemique postprandiale adaptee. La modulation de la digestibilite de l’amidon dans l’alimentation pourrait etre utilisee comme un outil nutritionnel simple chez le patient DT2 pour ameliorer l’homeostasie glucidique au quotidien.

International audience; Introduction: Causes of hyponatraemia in older patients are multivariate and in the case of SIADH may often be drug induced. Diagnostic and treatment algorithms are unclear for this important age group. Methods: The author group identified 6 broad themes for consensus and formulated 42 separate consensus statements within these 6 themes. Statements were then circulated to geriatricians, general practitioners and other doctors to test agreement at the European level. Results: 64 responses were evaluated from around Europe. Agreement was achieved in 86 % of the statements following amendment and redistribution of 6 of the statements. The survey and its feedback prompted the development of 13 recommendations related to the diagnosis and treatment of hyponatraemia including SIADH. Conclusion: The series of 13 recommendations developed here is intended to increase clarity for clinicians managing older patients with hyponatraemia and SIADH. Surprisingly, despite the lack of clear guidelines or recommendations for this age group consensus levels for the author-based statements were high among the respondents.

Resume La reduction manuelle des deplacements secondaires des fractures metaphysaires distales du radius n’est aisee que pendant les premiers dix a 15 jours suivant le traumatisme, avant l’apparition d’un cal. Quand la reduction est rendue impossible par un cal solide, une osteotomie a foyer ouvert est alors indiquee. Nous proposons une technique moins invasive dont l’objectif est de corriger un cal vicieux des que la reduction manuelle n’est plus possible : le calloclasis percutane. Il est realise sous amplificateur de brillance par perforations du cal en timbre-poste avec une broche de fort calibre, a distance du cartilage de croissance. Quand l’os est suffisamment fragilise, la reduction est obtenue en utilisant la broche comme levier intrafocal. La broche est alors fichee dans le cortex oppose pour assurer une stabilisation posterolaterale. Vingt-et-un patients ont ete traites selon cette technique avec de bons resultats, sans aucune complication. Cette technique permet un traitement peu agressif des cals vicieux et peut etre realisee de deux a six semaines apres le traumatisme. Niveau de preuve IV. Etude retrospective multicentrique.

Introduction Les pathologies cardiovasculaires representent desormais la premiere cause de mortalite au cours des maladies inflammatoires chroniques comme le lupus erythemateux systemique ou la polyarthrite rhumatoide. Ce surrisque cardiovasculaire est lie a l’inflammation chronique et aux therapeutiques (corticoides). Les donnees sur la morbi/mortalite cardiovasculaire chez les patients atteints de sclerodermie systemique sont rares et l’atteinte est souvent consideree comme purement microvasculaire. Mais de nombreuses publications rapportent des atteintes macrovasculaires comme des accidents vasculaires cerebraux. Notre objectif est donc de decrire la prevalence et l’incidence des accidents vasculaires au sein d‘une cohorte de patients atteints de sclerodermie systemique. Patients et methodes C’est a partir d’un PHRC regional, ou sont suivis 600 patients atteints de maladies inflammatoires chroniques de facon prospective qu’une etude descriptive a ete realisee chez des patients de Rhone-Alpes atteints de sclerodermie systemique. Pendant 10 ans, on a mesure la survenue d’evenements cardiovasculaires (CV), qu’il s’agisse d’un deces d’origine CV, d’un syndrome coronarien aigu, d’un accident vasculaire cerebral (AVC), d’une ischemie vasculaire, d’une insuffisance cardiaque ou encore d’une maladie thromboembolique. Resultats Cents patients furent inclus dont 79 femmes. L’âge moyen au moment de l’inclusion etait de 53,22 ans (DS 13,28). Au niveau des facteurs de risque CV connus, 18 patients etaient traites pour une hypertension arterielle (HTA), 27 avaient une dyslipidemie traitee ou non, 21 avaient un tabagisme actif, 21 un tabagisme ancien sevre et 9 presentaient une predisposition hereditaire. Au cours du suivi, 18 patients ont ete affectes d’au moins 1 evenement CV dont 16 ont presente 1 seul evenement et 2 ont presente 2 evenements. Trois des onze deces survenus durant le suivi sont imputables a une origine CV. On note 1 episode d’ischemie mesenterique, 1 AVC, 4 etats d’insuffisance cardiaque, 5 episodes de troubles du rythme et 6 manifestations thromboemboliques. Discussion Notre etude confirme, d’une part, la forte mortalite de la sclerodermie systemique soit 11 % a 10 ans, dont pres d’un tiers sont d’origine CV. D’autre part, elle demontre que les facteurs de risque CV et les pathologies qui en decoulent sont frequemment retrouves chez ces patients. Conclusion Ces donnees encore meconnues, incitent a une surveillance rapprochee et a un controle de l’HTA ainsi que des parametres lipidiques chez ces patients ou les atteintes micro- et macrocirculatoires se cotoient.

Resume Propos Les granulomatoses renales (GR) sont des maladies rares dont la frequence est estimee entre 0,5 a 1,3 % des ponctions biopsies renales (PBR) realisees. Les GR restent peu etudiees dans la litterature et les modalites therapeutiques et evolutives sont mal connues. Methodes Nous avons analyse 44 observations de GR identifiees sur l’ensemble des PBR realisees entre 1984 et 2005 dans la region Rhone-Alpes. Resultats Notre population etait composee de 25 hommes et 19 femmes. L’âge moyen au diagnostic etait de 56 ans. Le delai diagnostic moyen etait de 11 mois. L’insuffisance renale etait severe avec une clairance de la creatinine moyenne de 24 mL/min, associee a une proteinurie dans 77 % des cas (taux moyen de 0,9 g/24 heures), et a une hematurie microscopique et une leucocyturie aseptique chez respectivement 30 et 25 % des patients. La sarcoidose etait la principale etiologie, dans 25 % des cas ( n = 11), suivie par l’origine immunoallergique (9 %, n = 4), la tuberculose (6,8 %, n = 3), les hemopathies (6,8 %, n = 3), l’infection par le virus de l’immunodeficience humaine ( n = 1) et le rejet chronique chez un transplante renal ( n = 1). La GR etait qualifiee d’idiopathique dans 48 % des cas ( n = 21). La severite de l’atteinte renale expliquait le recours frequent a l’epuration extra renale (34 %, n = 15). Trois patients ont justifie une greffe renale. L’evolution etait cependant plutot favorable : la fonction renale s’est finalement amelioree dans 41 % ( n = 18) et stabilisee dans 34 % des cas ( n = 15). Conclusions La sarcoidose, les causes medicamenteuses et infectieuses sont les causes les plus frequentes de GR. L’enquete diagnostique est compliquee par l’absence de donnees histologiques pathognomoniques sur la PBR. La corticotherapie est le traitement de reference des GR sarcoidosiques, immunoallergiques et idiopathiques. Autant que possible, le traitement est etiologique.

Resume Introduction Dans les stades 1 de toutes les classifications communement utilisees pour caracteriser le tibia vara infantile, le diagnostic differentiel avec le genu varum physiologique est difficile. Il n’existe pas de critere pronostique permettant de poser une indication therapeutique a ce stade. Patient et methodes Nous avons retrospectivement etudie une serie de 26 patients de la zone ocean Indien vus au stade 1, afin de savoir si certaines maladies de Blount pouvaient guerir sans traitement. Resultats Au terme de cette etude, il apparait que les maladies de Blount stade 1 ont environ une chance sur trois d’evoluer spontanement vers la guerison. Discussion Une classification plus fine en trois stades, pourrait alors permettre de mieux preciser les indications therapeutiques : stade 0 ou maladie de Blount possible (enfant d’âge superieur a 2,5 ans), stade 1 ou maladie de Blount certaine, physe active (+) (evolutivite, âge superieur a trois ans, image typique sans pont d’epiphysiodese), stade 2 ou maladie de Blount physe inactive (−) (epiphysiodese tibiale superomediale). Niveau d’evidence IV.