In chronic kidney disease, serum alpha-Klotho is related to serum bicarbonate and proteinuria

International audienceOBJECTIVES: Klotho is an "aging-suppressor" gene and encodes a single-pass transmembrane protein predominantly expressed in renal tubules. Whether chronic kidney disease (CKD) affects serum Klotho is poorly documented. We aimed to measure the relationship of serum alpha-Klotho with renal function, acid-base status, bone biomarkers, and proteinuria in CKD patients. DESIGN SETTING, PARTICIPANTS, AND MEASUREMENTS: We measured serum alpha-Klotho, serum FGF23, and glomerular filtration rate by inulin clearance in 60 CKD patients between January and July 2011. We also measured serum creatinine, bicarbonate, calcium, phosphorus, parathyroid hormone, C-reactive protein, and 25-OH vitamin D. Proteinuria was obtained from a 24-h urine collection. RESULTS: The median serum alpha-Klotho was 478 (348-658) pg/mL. We found an inverse relationship between serum alpha-Klotho and serum creatinine (r = -0.36, P = .007), proteinuria (r = -0.36, P = .013), and a positive relationship with serum bicarbonate (r = 0.33, P = .011). There was no further significant relation between serum alpha-Klotho and inulin clearance or serum FGF23. Multiple regression analysis including serum bicarbonate, serum creatinine, and proteinuria indicated that only serum bicarbonate was associated with serum alpha-Klotho (P = .003). CONCLUSIONS: This study shows that in CKD, serum alpha-Klotho is related to serum bicarbonate and proteinuria and not to renal function. Further research is required to determine whether correcting these 2 amenable conditions would improve serum alpha-Klotho

Establishment of reference values of alpha-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia

International audienceBACKGROUND: Chylomicron retention disease (CMRD), a rare genetic hypocholesterolemia, results in neuro-ophtalmologic damages, which can be prevented by high doses of vitamin E during infancy. In these patients, plasma vitamin E concentration is significantly reduced due to defects of chylomicron secretion. Vitamin E in adipose tissue (AT) and red blood cells (RBC) have been proposed as potential relevant biomarkers of vitamin E status but no reference values in children are available. The objectives were (i) to establish age-reference intervals in healthy children for alpha-tocopherol in plasma, red blood cells (RBC) and adipose tissue (AT) and (ii) to determine the variations of alpha-tocopherol in patients with CMRD after oral treatment with vitamin E. METHODS: This prospective study included 166 healthy children (1 month - 18 years) and 4 patients with CMRD. Blood and AT were collected in healthy children during a scheduled surgery and in patients before and after a 4-month treatment with alpha-tocopherol acetate. RESULTS: The reference ranges for alpha-tocopherol were 11.9 - 30 mumol/L in plasma, 2.0 - 7.8 mumol/L packed cells in RBC and 60 - 573 nmol/g in AT. alpha-tocopherol levels in plasma correlated with those of RBC (r = 0.31; p \textless 0.01). In patients with CMRD after 4 months treatment, alpha-tocopherol concentrations remained less than 70 % of the control values in plasma, increased by 180 % to reach normal values in RBC, and remained stable in the normal range in AT. CONCLUSION: This study establishes pediatric reference intervals for alpha-tocopherol in plasma, RBC and AT. These values will be beneficial in assessing accurate alpha-tocopherol status in children and to optimize the monitoring of rare diseases such as CMRD. Our data suggest that RBC alpha-tocopherol, appears as a relevant biomarker to appreciate the effectiveness of treatment with alpha-tocopherol in patients with a rare primary hypocholesterolemia. The biopsy of AT could be used at diagnosis to assess the severity of the vitamin E deficiency and periodically after a long duration of vitamin E therapy to assess whether the treatment is effective, based on reference intervals defined in this study

First hospitalization for heart failure in France in 2009: patient characteristics and 30-day follow-up

SummaryBackgroundThe incidence of heart failure (HF) is stable in industrialized countries, but its prevalence continues to increase, especially due to the ageing of the population, and mortality remains high.ObjectiveTo estimate the incidence in France and describe the management and short-term outcome of patients hospitalized for HF for the first time.MethodThe study population comprised French national health insurance general scheme beneficiaries (77% of the French population) hospitalized in 2009 with a principal diagnosis of HF after exclusion of those hospitalized for HF between 2006 and 2008 or with a chronic disease status for HF. Data were collected from the national health insurance information system (SNIIRAM).ResultsA total of 69,958 patients (mean age 78years; 48% men) were included. The incidence of first hospitalization for HF was 0.14% (≥55years, 0.5%; ≥90years, 3.1%). Compared with controls without HF, patients more frequently presented cardiovascular or other co-morbidities. The hospital mortality rate was 6.4% and the mortality rate during the 30days after discharge was 4.4% (3.4% without readmission). Among 30-day survivors, all-cause and HF 30-day readmission rates were 18% (<70years, 22%; ≥90years, 13%) and 5%, respectively. Reimbursements among 30-day survivors comprised at least a beta-blocker in 54% of cases, diuretics in 85%, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in 67%, a diuretic and ACEI/ARB combination in 23% and a beta-blocker, ACEI/ARB and diuretic combination in 37%.ConclusionPatients admitted for HF presented high rates of co-morbidity, readmission and death at 30days, and there remains room for improvement in their drug treatments; these findings indicate the need for improvement in return-home and therapeutic education programmes

Low Levels of Fecal Calprotectin 3 Months After Surgery Predict Subsequent Endoscopic Postoperative Remission in Crohn's Disease

International audienceBACKGROUND/AIMS: In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection. METHODS: In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC. Endoscopic POR was assessed by ileocolonoscopy within 6-12 months (median 7 months). Receiver operating characteristic (ROC) curves were generated to assess accuracy of the markers, to determine the best threshold and to calculate sensitivity, specificity, positive and negative predictive values. RESULTS: In contrast with median CRP levels, median FC concentrations measured 3 months after surgery were significantly higher in patients who later experienced endoscopic POR (Rutgeerts ≥ i2) compared with those who stayed in endoscopic remission within the following 6-12 months (205 μg/g IQR [106-721] vs. 103 μg/g IQR [60-219], p = 0.008). Area under the ROC curve for FC was 0.71. The best cutoff value of FC to identify patients in subsequent endoscopic remission 3 months after surgery was 65 μg/g (96% sensitivity, 31% specificity, 50% positive and 91% negative predictive values). In multivariate analysis, FC \textless 65 µg/g at 3 months was the only factor associated with subsequent endoscopic remission. CONCLUSION: FC measured 3 months after surgery below 65 μg/g is an accurate marker to identify CD patients who will later stay in endoscopic remission within 1 year after resection

[Mutltifaceted biological roles of leptin]

International audienceThe identification of leptin allowed the discovery of a new endocrine system. This major adipokine controlling energy homeostasis is also involved in the regulation of neuroendocrine function and fertility. Unfortunately, leptin is not able to treat common obesity, which associates hyperleptinemia and resistance to the hormone. Conversely, treatment with recombinant leptin is effective in situations of leptin deficiency. Several pathophysiological situations associated with adipose tissue dysfunctions and abnormal regulation of leptin secretion are discussed in this review. The advantage of the potential use of the leptin assay in some pathophysiological conditions is proposed

Rôles biologiques à multiples facettes de l’adiponectine

International audienceAdiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.L’adiponectine est une adipokine majeure de l’homéostasie énergétique qui présente des propriétés insulino-sensibilisatrices. Elle est diminuée dans les états de résistance à l’insuline et est associée négativement à plusieurs situations physiopathologiques dont l’obésité abdominale, le syndrome métabolique, la stéatose et la stéato-hépatite non alcoolique, le diabète de type 2, certains cancers et des maladies cognitives. Ces aspects sont discutés dans cette revue

Delta Hemolysin and Phenol-Soluble Modulins, but Not Alpha Hemolysin or Panton-Valentine Leukocidin, Induce Mast Cell Activation

International audienceMast cells are located at host interfaces, such as the skin, and contribute to the first-line defense against pathogens by releasing soluble mediators, including those that induce itching and scratching behavior. Here, we show that delta-hemolysin (Hld) and phenol soluble modulins (PSMs) PSMα1 and PSMα3, but not alpha-hemolysin (Hla) or Panton-Valentine leukocidin (PVL), induce dose-dependent tryptase, and lactate dehydrogenase (LDH) release by the HMC-1 human mast cell line. Using supernatants from isogenic strains, we verified that tryptase and LDH release was Hld- and PSMα-dependent. PSMα1 and Hld production was detected in 65 and 17% of human Staphylococcus aureus-infected skin abscess specimens, respectively, but they were produced in vitro by all clinical isolates. The results suggest that Hld and PSM-α1 produced in vivo during S. aureus skin infections induce the release of mast cell mediators responsible for itching and scratching behavior, which may enhance skin to skin transmission of S. aureus via the hands. As Hld and PSMs are upregulated by accessory gene regulator (agr), their association may contribute to the elective transmission of S. aureus strains with a functional agr system

Normal serum ApoB48 and red cells vitamin E concentrations after supplementation in a novel compound heterozygous case of abetalipoproteinemia

International audienceBACKGROUND AND AIMS: Abetalipoproteinemia (ABL) is a rare recessive monogenic disease due to MTTP (microsomal triglyceride transfer protein) mutations leading to the absence of plasma apoB-containing lipoproteins. Here we characterize a new ABL case with usual clinical phenotype, hypocholesterolemia, hypotriglyceridemia but normal serum apolipoprotein B48 (apoB48) and red blood cell vitamin E concentrations. METHODS: Histology and MTP activity measurements were performed on intestinal biopsies. Mutations in MTTP were identified by Sanger sequencing, quantitative digital droplet and long-range PCR. Functional consequences of the variants were studied in vitro using a minigene splicing assay, measurement of MTP activity and apoB48 secretion. RESULTS: Intestinal steatosis and the absence of measurable lipid transfer activity in intestinal protein extract supported the diagnosis of ABL. A novel MTTP c.1868G\textgreaterT variant inherited from the patient's father was identified. This variant gives rise to three mRNA transcripts: one normally spliced, found at a low frequency in intestinal biopsy, carrying the p.(Arg623Leu) missense variant, producing in vitro 65% of normal MTP activity and apoB48 secretion, and two abnormally spliced transcripts resulting in a non-functional MTP protein. Digital droplet PCR and long-range sequencing revealed a previously described c.1067+1217\₁141del allele inherited from the mother, removing exon 10. Thus, the patient is compound heterozygous for two dysfunctional MTTP alleles. The p.(Arg623Leu) variant may maintain residual secretion of apoB48. CONCLUSIONS: Complex cases of primary dyslipidemia require the use of a cascade of different methodologies to establish the diagnosis in patients with non-classical biological phenotypes and provide better knowledge on the regulation of lipid metabolism