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

Benzylthiouracil-induced ANCA-associated Vasculitis: A Case Report and Literature Review

Iatrogenic antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is not exceptional. Many cases of small vessel vasculitis induced by anti-thyroid drugs (ATD), mainly propylthiouracil (PTU), have been reported. We present a case of AAV related to another ATD: benzylthiouracil (BTU) and review the literature. An 84-year-old man with a 4-year history of multinodular goitre with hyperthyroidism was treated with BTU. He presented an acute syndrome with weakness, fever, epigastric pain and abdominal distension. Lactate and lipase tests were normal. An abdominal scan showed a thrombosis of the splenic artery with splenic infarction. We excluded a hypothesis of associated embolic aetiology: atrial fibrillation, atrial myxoma, intraventricular thrombus or artery aneurysm. Exploration of a possible prothrombotic state (complete blood count, haemostasis tests, activated protein C resistance, factor V Leiden, protein C, S, antithrombin III) gave normal results. Tests for antinuclear antibodies (ANA) and antiphospholipid antibodies (APL) were negative. However, testing for p-ANCA, with antimyeloperoxidase (MPO) specificity, was positive: 120.6 CU (N<20.0). We did not find other systemic manifestations, except a non-specific kidney failure. BTU was discontinued without steroids or immune-modulating drugs. Subsequently, symptoms disappeared progressively and titres of ANCA fell until normalization, 4 months later. Many patients treated with BTU present a high prevalence of ANCA, mainly, but not exclusively, directed against MPO. Vasculitis, however, remains an uncommon complication. The mechanism of this anomaly remains to be elucidated. Some studies suggest the possibility of an autoimmune reaction initiated by drug bioactivation mediated by neutrophil-derived MPO. The present observation is particular because the involved drug was BTU and clinical expression was unusual

Viscerotropic disease: case definition and guidelines for collection, analysis, and presentation of immunization safety data

Viscerotropic disease (VTD) is defined as acute multiple organ system dysfunction that occurs following vaccination. The severity of VTD ranges from relatively mild multisystem disease to severe multiple organ system failure and death. The term VTD was first used shortly after the initial published reports in 2001 of febrile multiple organ system failure following yellow fever (YF) vaccination. To date, VTD has been reported only in association with YF vaccine and has been thus referred to as YF vaccine-associated viscerotropic disease (YEL-AVD)

BCGites, histoire d'une suspension d'obligation vaccinale (à propos de l'expérience rouennaise)

En 1921, la France voit naître la vaccination antituberculeuse dont la mise en oeuvre va permettre d'épargner de nombreuses vies, notamment chez les jeunes enfants. Alors que nombre de nos voisins européens ont abandonné la vaccination systématique, celle-ci va se maintenir sur le territoire national jusqu'en juillet 2007. La multiplication des notifications de cas de BCGites, qui fait suite au changement de spécialité vaccinale à partir de 2006, accélère la réflexion sur la politique vaccinale en France qui aboutie à la modification des recommandations officielles. Le but de ce travail, était de répertorier l'ensemble des cas d'effets indésirables mettant en cause le vaccin BCG SSI®, notifiés au centre régional de pharmacovigilance de Rouen sur la période allant du le janvier au 31 décembre 2006. Au travers de l'examen de ces dossiers, nous souhaitions nous intéresser aux particularités de ces effets indésirables et des facteurs favorisant leur survenue, susceptibles d'expliquer leur impact sur la politique de vaccination. L'analyse des 56 cas recueillis, confirme l'importance de ces réactions indésirables et retrouve un important mésusage à l'origine d'une part de ces cas, justifiant des mesures d'informations renforcées. En mettant en exergue, la difficulté de prise en charge de certains de ces cas d'abcès et le nombre non négligeable de séquelles esthétiques induites, elle permet de mieux comprendre la remise en cause de la balance bénéfice/risque.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Les Acidoses lactiques en cours de traitement par Metformine (bilan de pharmacovigilance en Haute-Normandie)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

An obituary for GFR as the main marker for kidney function?

This publication comments on the recently published findings of a study by Eloot etal. (cJASN, 6: 12661273, 2011) that evaluated the correlation between several formulae for calculating estimated GFR (eGFR) and different low molecular weight uremic toxins; eGFRs were based on serum creatinine (SCrea), cystatin C (Cys C), or a combination of both. Unexpectedly, the correlations for the different solutes were highly inconsistent, irrespective of the eGFR formula. On the other hand, the different eGFR formulae gave consistent results per solute. Correlation coefficients for some solutes were low (hippuric acid, p-cresylsulfate, indole acetic acid, uric acid, asymmetric dimethylarginine) to nonsignificant (carboxy-methyl-propyl-furanpropionic acid). These data point to the fact that eGFR is a deceiving predictor of uremic solute concentration and their biological action; this inconsistency is very likely the result of the impact of other factors affecting concentration, such as tubular secretion, generation by intestinal flora and metabolism

The expanding roles of microRNAs in kidney pathophysiology

International audienc