Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?

Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?BackgroundIn clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population.MethodsFive hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method).ResultsEach GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40mL/min/1.73m2 apart. The proportion of predicted GFR differing from inulin clearance by ± 10mL/min/1.73m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one.ConclusionNone of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement

Spectrum of ANCA-Associated Disorders According to Serological Phenotype in Routine Care: Retrospective Case Series of 209 Patients

Objective: To summarize the experience of three years of positive ANCA (anti-neutrophil cytoplasmic antibodies) testing in a single university based hospital. We describe the clinical features according to ANCA phenotype of patients who did and did not have ANCA- associated vasculitis (AAV).Methods: We did a review of all samples tested for ANCA in a 3 year-period (2005-2007). Each sample was tested by indirect immunofluorescence (IIF) and enzyme-linked-immunosorbent assay (ELISA). Sera were considered as positive for ANCA testing if either IIF or ELISA for MPO or PR3 antigen specificity was positive. Patients were considered as having AAV on established diagnostic criteria and algorithms.Results: The positive ANCA population consisted in 209 patients, 54 were classified in the AAV group and 155 patients constituted the “Others†group. The typically most relevant ANCA phenotypes (C-ANCA/anti-PR3+ and P-ANCA/anti-MPO+) were detected in 90 % (49/54) of patients in the AAV group and only 10% (15/155) of the “Others†group (p &lt; 0.001). Among the latter none developed AAV during follow-up. Positive IIF alone was found in 4% (2/54) of the AAV group and in 68% (105/155) of the “Others†group (p &lt; 0.001). In patients without AAV, positive IIF alone or positive ELISA with negative IIF represented the main ANCA pattern.Conclusion: In routine clinical practice, most patients with positive ANCA testing do not have AAV. The typical ANCA pattern (C-ANCA/anti-PR3+ or P-ANCA/anti-MPO+) remains a strong predictor of AAV in patients with a high level of suspicion for systemic vasculitis. In other cases, ANCA positivity should be interpreted with extreme caution

Immunomonitoring du rituximab appliqué aux maladies auto-immunes : une aide pour la pratique clinique ?

International audienceIntroductionImmune monitoring of monoclonal antibodies is a helpful tool in optimizing the management of patients treated with TNF blockers, especially in gastroenterology. In contrast, studies evaluating the interest of such monitoring are lacking for other monoclonal antibodies used in autoimmune diseases, including rituximab despite its widespread use in the field for almost 15 years. Hence, we conducted a study whose goal was to describe the clinical and biological characteristics of all patients who had a rituximab immune monitoring.MethodsAll the clinical, biological and therapeutic data attached to the demands (from 2015 onwards) we received for immune monitoring of rituximab (measurements of rituximab serum levels and anti-rituximab antibodies using the drug-sensitive assay LISA-TRACKER Duo Rituximab®), were retrospectively reviewed. Suspected cases of hypersensitivity and secondary non-response were included.ResultsSeveral medical specialities (nephrology, haematology, neurology, rheumatology, internal medicine) were represented among the 18 records included in the study (out of 23 demands), 10 being suspected cases of hypersensitivity and 8 secondary non-responders. All 6 patients whose symptoms were consistent with the classical presentation of serum sickness, as well as half of the secondary non-responders, were positive for antirituximab antibodies.ConclusionThis detailed real world case study illustrates the potential benefits of rituximab immune monitoring (especially anti-rituximab antibodies) in autoimmune diseases, suggesting it could be helpful in suspected cases of serum sickness, as well as secondary non-response (B-cell non-depletion being an early red flag). Larger and disease-specific studies are warranted to support these findings.IntroductionL’immunomonitoring des anticorps monoclonaux représente une aide pour la prise en charge des patients sous anti-Tumor Necrosis Factor-α, en particulier en gastro-entérologie. En revanche, pour les autres anticorps monoclonaux, dont le rituximab, pourtant utilisé depuis près de quinze ans en auto-immunité, les études évaluant l’intérêt de ce monitoring sont quasiment absentes. Ainsi, l’objectif de cette étude était de décrire les caractéristiques clinicobiologiques des patients pour lesquels un immunomonitoring du rituximab a été prescrit dans notre centre.MéthodesLes données cliniques, biologiques et thérapeutiques disponibles pour les demandes d’immunomonitoring du rituximab (dosages de la rituximabémie et des anticorps antirituximab par une technique « sensible au médicament » LISA-TRACKER Duo Rituximab®) reçues depuis 2015 ont été analysées rétrospectivement. Les suspicions d’hypersensibilité et les non-réponses secondaires ont été incluses.RésultatsSur les 23 demandes reçues, 18 dossiers ont été inclus, impliquant plusieurs spécialités (néphrologie, hématologie, neurologie, rhumatologie, médecine interne), avec 10 suspicions d’hypersensibilité et 8 non-réponses secondaires. Les 6 patients dont la présentation clinique était évocatrice de maladie sérique, ainsi que la moitié des cas de non-réponse secondaire, étaient positifs pour les anticorps anti-rituximab.ConclusionL’analyse des différentes situations cliniques présentées ici ayant conduit à une demande d’immunomonitoring du rituximab suggère que cet examen (en particulier la recherche d’anticorps antirituximab) serait intéressant en cas de suspicion de maladie sérique et/ou de non-réponse secondaire (notamment en l’absence de déplétion lymphocytaire B), et mériterait d’être étudié via des études prospectives de grande taille

Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis

International audienceHeparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess non-inferiority of a heparin grafted dialyzer (NCT01318486). A total of 251 maintenance hemodialysis patients at increased risk of hemorrhage were randomly allocated for up to three heparin-free hemodialysis sessions using a heparin-grafted dialyzer or the center standard-of-care consisting of regular saline flushes or pre-dilution. The first heparin-free hemodialysis session was considered successful when there was neither complete occlusion of air traps or dialyzer, nor additional saline flushes, changes of dialyzer or bloodlines, or premature termination. The current standard-of-care resulted in high failure rates (50%). The success rate in the heparin-grafted membrane arm was significantly higher than in the control group (68.5% versus 50.4%), which was consistent for both standard-of-care modalities. The absolute difference between the heparin-grafted membrane and the controls was 18.2%, with a lower bound of the 90% confidence interval equal to plus 7.9%. The hypothesis of the non-inferiority at the minus 15% level was accepted, although superiority at the plus 15% level was not reached. Thus, use of a heparin-grafted membrane is a safe, helpful, and easy-to-use method for heparin-free hemodialysis in patients at increased risk of hemorrhage

A RANDOMIZED CONTROLLED MULTICENTER TRIAL OF A HEPARIN-GRAFTED POLYACRYLONITRILE MEMBRANE FOR NO-HEPARIN HEMODIALYSIS VERSUS STANDARD-OF-CARE: RESULTS OF THE HEPZERO STUDY

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Treatment tolerance and patient-reported outcomes favor online hemodiafiltration compared to high-flux hemodialysis in the elderly

International audienc