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Hôpital-Camfrout, France

Kuster N.,Montpellier University Hospital Center | Cristol J.-P.,Montpellier University Hospital Center | Cavalier E.,University of Liege | Bargnoux A.-S.,Montpellier University Hospital Center | And 4 more authors.
Clinica Chimica Acta | Year: 2014

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 60mL/min/1.73m2 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 90mL/min/1.73m2, 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 90mL/min/1.73m2.Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90mL/min/1.73m2 with MDRD and 120mL/min/1.73m2 with CKD-EPI equation. © 2013 Elsevier B.V.

Boutten A.,Biochimie | Bargnoux A.-S.,Montpellier University Hospital Center | Carlier M.-C.,Biochimie | Delanaye P.,University of Liege | And 7 more authors.
Clinica Chimica Acta | Year: 2013

The French Society of Clinical Biochemistry conducted this study to compare the accuracy and performances of the best creatinine enzymatic assays and the compensated Jaffe methods from the same manufacturers. Creatinine was measured in 3 serum pools with creatinine levels of 35.9 ± 0.9 μmol/L, 74.4 ± 1.4 μmol/L, and 97.9 ± 1.7 μmol/L (IDMS determination). The performances of the assays (total error that includes the contribution of bias and imprecision) were evaluated using Monte-Carlo simulations and compared against desirable NKDEP criteria.The enzymatic assays always fell within the desirable total Error of 7.6%. By contrast, this requirement was never obtained for the compensated Jaffe methods at the critical level of 74.4 ± 1.4 μmol/L. Only the compensated Jaffe creatinine on Olympus analyzer reached this specification at 35.9 ± 0.9 and 97.9 ± 1.7 μmol/L levels. This study demonstrates that, despite substantial improvement regarding traceability to the IDMS reference method and precision, compensated Jaffe creatinine methods, by contrast to enzymatic ones, do not reach the desirable specifications of NKDEP at normal levels of creatinine. © 2013.

Boutron A.,Hopitaux universitaires Paris Sud | Labarthe F.,Pediatrie metabolique | Lamireau D.,Reanimation Pediatrique | de Villemeur T.B.,Neuropediatrie | And 3 more authors.
Molecular Genetics and Metabolism | Year: 2011

Background: Deficiency of mitochondrial trifunctional protein (MTP) is caused by mutations in the HADHA and HADHB genes, which have been mostly delineated at the genomic DNA level and have not been always elucidated. Aim: To identify mutations in a French cohort of 52 MTP deficient patients and the susceptibility of mutations generating premature termination codons (PTCs) to the nonsense mRNA mediated decay (NMD). Methods: Mutation screening in fibroblasts was performed at the cDNA level and real-time RT-PCR was used to compare the levels of the different PTC-bearing mRNAs before and after a treatment of fibroblasts by emetine, a translation inhibitor. Results: A mutation detection rate of 100% was achieved. A total of 22 novel mutations were identified, including a large-sized genomic deletion in HADHB gene. A high proportion of all identified mutations were non-sense, frameshift and splicing mutations, generating (PTCs), distributed essentially on HADHA coding regions. We could demonstrate that the majority of mutations resulting in PTCs conform to the established rules governing the susceptibility to NMD. Conclusion: Our results emphasize the value of cDNA analysis in the characterization of HADHA and HADHB mutations and further strengthen the model of haploinsufficiency as a major pathomechanism in MTP defects. © 2011 Elsevier Inc.

We have evaluated the methodological quality of the Rémic (microbiology guidelines - bacteriology and mycology) of the Société Française de Microbiologie 2007, using to AGREE criteria, which are consensual at an international level, in particular at the the WHO (World Health Organisation) and at the European Union. The methodological quality of the Rémic is sub-optimal. These shortcomings in quality are mainly observed in AGREE domain n° 5 (applicability), in AGREE item n° 5 (patients' opinions were not considered), and in AGREE item n° 23 (conflicts of interest were not declared). The users of the Rémic must be aware of these few methodological shortcomings in order for them to be careful before they put its recommendation in practice. In conclusion, we advise the editors of the Rémic to insert at least a methodological chapter in their next édition. © 2011 Springer Verlag France.

Corcia P.,University of Tours | Bensimon G.,University Pierre and Marie Curie | Pieroni L.,Biochimie Metabolique
PLoS ONE | Year: 2012

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the loss of motor neurons. Its etiology remains unknown, but several hypothesis have been raised to explain motor neuron death, including oxidative stress. Dysregulation of cellular iron metabolism can lead to increased oxidative stress, and existing data argue for a role of iron metabolism in ALS pathophysiology. Methods: We performed a retrospective analysis of iron metabolism (IM) variables (serum levels of iron, transferrin, ferritin, and TSC for Transferrin Saturation Coefficient) in a cohort of 694 ALS patients and 297 healthy controls. Results: Serum ferritin levels and TSC were higher, whereas serum transferrin levels were lower in ALS patients than controls. In addition, patients with a high level serum ferritin had a shorter survival time compared to those with low level serum ferritin (618 days versus 921 days for men subgroup; p =. 007). Site of onset and ALS-FRS score were not associated with IM variables. Conclusion: This study suggests that ALS patients may have increased iron storage, as measured by increased serum ferritin and TSC. Elevated serum ferritin may also have a deleterious impact on survival in ALS. © 2012 Nadjar et al.

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