Enzymatic creatinine assays allowestimation of glomerular filtration rate in stages 1 and 2 chronic kidney disease using CKD-EPI equation

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m2 should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24 084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m2, both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m2. Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m2 with MDRD and 120 mL/min/1.73 m2 with CKD-EPI equation.Peer reviewe

A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial)

To assess the efficacy of the interleukin 1 receptor antagonist anakinra in systemic-onset juvenile idiopathic arthritis (SJIA).status: publishe

Induction of Heme Oxygenase-1, Biliverdin Reductase and H-Ferritin in Lung Macrophage in Smokers with Primary Spontaneous Pneumothorax: Role of HIF-1α

Few data concern the pathophysiology of primary spontaneous pneumothorax (PSP), which is associated with alveolar hypoxia/reoxygenation. This study tested the hypothesis that PSP is associated with oxidative stress in lung macrophages. We analysed expression of the oxidative stress marker 4-HNE; the antioxidant and anti-inflammatory proteins heme oxygenase-1 (HO-1), biliverdin reductase (BVR) and heavy chain of ferritin (H-ferritin); and the transcription factors controlling their expression Nrf2 and HIF-1alpha, in lung samples from smoker and nonsmoker patients with PSP (PSP-S and PSP-NS), cigarette smoke being a risk factor of recurrence of the disease.mRNA was assessed by RT-PCR and proteins by western blot, immunohistochemistry and confocal laser analysis. 4-HNE, HO-1, BVR and H-ferritin were increased in macrophages from PSP-S as compared to PSP-NS and controls (C). HO-1 increase was associated with increased expression of HIF-1alpha mRNA and protein in alveolar macrophages in PSP-S patients, whereas Nrf2 was not modified. To understand the regulation of HO-1, BVR and H-ferritin, THP-1 macrophages were exposed to conditions mimicking conditions in C, PSP-S and PSP-NS patients: cigarette smoke condensate (CS) or air exposure followed or not by hypoxia/reoxygenation. Silencing RNA experiments confirmed that HIF-1alpha nuclear translocation was responsible for HO-1, BVR and H-ferritin induction mediated by CS and hypoxia/reoxygenation.PSP in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1alpha-mediated induction of HO-1, BVR and H-ferritin

Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema

BACKGROUND: Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. METHODS: Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. RESULTS: Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. CONCLUSION: The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers

Actualités sur les méthodes de référence pour le dosage des protéines urinaires

International audienceMeasurement of urine albumin has been introduced in the new classification of kidney disease (KD) as a marker for detecting, monitoring and predicting KD. Currently, the measure is not standardized. The variability of results obtained with commercially available procedures is important and can lead to misclassification of patients. Analytical standardization, started in 2007, is in progress. SRM 2925 primary reference material, SRM 3666 secondary reference material and liquid chromatography isotope dilution mass spectroscopy (LC-IDMS) reference measurement procedure are being validated by the National Institute of Standards and Technology (NIST). This report presents strategies and difficulties for developing this reference system.La mesure de la microalbuminurie a été introduite dans la nouvelle classification de la maladie rénale (MR) comme marqueur pour le dépistage, le suivi et la prédiction du risque. Actuellement la mesure est non standardisée.La variabilité des résultats obtenus avec différentes trousses commercialisées est importante et peut entraîner des erreurs de classification des patients. La standardisation analytique, débutée en 2007, progresse. Un matériau de référence primaire SRM 2925, un matériau de référence secondaire SRM 3666et une méthode de mesure de référence, la chromatographie liquide couplée à la spectrométrie de masse avec dilution isotopique (LC-IDMS), sont en cours de validation au National institute of standards and technology(NIST). Cet article présente les stratégies et les difficultés pour mettre au point ce système de référence

La voie Nrf2 en pathologie respiratoire

Les voies respiratoires sont la première cible des oxydants inhalés (polluants atmosphériques) ou générés localement par les cellules médiatrices de la réponse inflammatoires. Pour faire face à ces agressions, le poumon possède des défenses antioxydantes. Le facteur de transcription nuclear factor erythroid-2-related factor 2 (Nrf2) contrôle l’expression des gènes antioxydants et cytoprotecteurs via la séquence régulatrice appelée élément de réponse antioxydant (ARE). Le stress oxydant et la voie de signalisation Nrf2/Keap1-Bach1 ont un rôle essentiel dans la physiopathologie de nombreuses pathologies respiratoires aiguës et chroniques. La voie Nrf2 participe à la protection pulmonaire au cours de la bronchopneumopathie chronique obstructive, l’emphysème, l’asthme, la fibrose et les agressions pulmonaires aiguës. Nous présentons dans cette revue les données récentes concernant les mécanismes de la protection pulmonaire induite par Nrf2 et l’intérêt potentiel d’une thérapeutique ciblant ce facteur

Recommandations pour le choix et l'harmonisation des techniques de dosage de la créatinine

En 2010, un groupe de travail mixte constitué de la Société française de biologie clinique (SFBC) et de la Société de nephrologie (SN) a formulé les propositions suivantes afin de réactualiser les recommanadations pour le dosage de la créatinine plasmatique

Modeling changes in biomarkers in Gaucher disease patients receiving enzyme replacement therapy using a pathophysiological model

Gaucher disease (GD) is a rare recessively inherited disorder caused by deficiency of a lysosomal enzyme, glucocerebrosidase. Accumulation of glucosylceramide or glucosylsphingosine in macrophages leads to increased production of ferritin and chitotriosidase and to decreases in hemoglobin concentration and platelet count, which are used as blood biomarkers. GD is treated by enzyme replacement therapy (ERT) or, sometimes by substrate reduction therapy. However, no physiological model for analysis of biomarkers change during ERT has been proposed. We aimed to develop a pathophysiological model to analyze biomarker's response to ERT and several covariates impact

Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial

International audienceBackground: In sepsis, neutrophil respiratory bursts participate in endothelium damage, the first step to multiple organ failure. In plasma two antioxidant selenoenzymes, which protect the endothelium, decrease: selenoprotein-P, and to a lesser extent glutathione peroxidase (GPX3). Sodium selenite (Na2SeO3) is a Se donor, but also an oxidant chemotherapy drug depending on its concentration. In a previous published study, Na(2)SeO(3 )continuous infusion in septic shock patients at a pharmacological dose of 4 mg1 Se/day on day-1, followed by a high nutritional dose of 1 mg Se/day during 9 days, showed no beneficial effect on weaning of catecholamine nor on survival. In this ancillary study, we report clinical and biological effects of such continuous infusion of Na2SeO3. Methods: This was a multicenter, placebo-controlled, double-blind study on 60 patients. Na(2)SeO(3)or placebo in continuous infusion as described above. Evolution with time of plasma Se, selenoprotein-P, GPX(3), Organ dysfunction (sequential organ failure assessment SOFA scores, including PaO2/FiO(2), for respiratory failure, and plasma lactate) and quality of life at 6 months (by SF36 scores) were analyzed using two-way (time, treatment) non-parametric repeated-measures analysis of variance (Friedman test). Main Results: At baseline, plasma Se was about a quarter of reference values. From baseline to day-4 plasma Se, selenoprotein-P and GPX(3) significantly increased by 3.9, 2.7 and 1.8 respectively in the Na(2)SeO(3 )group as compared with placebo and remained elevated by 2.3, 2.7 and 2.1 at day-14 respectively (p < 0.001). Na(2)SeO(3 )did not affect global and organ by organ SOFA Scores and plasma lactate concentration at day-1 and later up to day-14. The evolution of PaO2/FiO(2) until day-14 was similar in the two groups. Quality of life in the surviving patients at 6 months was similar between the two groups. Conclusion: Continuous infusion of Na(2)SeO(3 )at 4 mg Se at day-1 seems to have neither beneficial nor toxic effect at day-1 or later and induces a late increase of selenoprotein-P at day-4. Preclinical studies are required to confirm the use of Na(2)SeO(3 )as a cytotoxic drug against neutrophils and protection of the endothelium by sele-noprotein-P