C5b9 Deposition in Glomerular Capillaries Is Associated With Poor Kidney Allograft Survival in Antibody-Mediated Rejection

C4d deposition in peritubular capillaries (PTC) reflects complement activation in antibody-mediated rejection (ABMR) of kidney allograft. However, its association with allograft survival is controversial. We hypothesized that capillary deposition of C5b9—indicative of complement-mediated injury—is a severity marker of ABMR. This pilot study aimed to determine the frequency, location and prognostic impact of these deposits in ABMR. We retrospectively selected patients diagnosed with ABMR in two French transplantation centers from January 2005 to December 2014 and performed C4d and C5b9 staining by immunohistochemistry. Fifty-four patients were included. Median follow-up was 52.5 (34.25–73.5) months. Thirteen patients (24%) had C5b9 deposits along glomerular capillaries (GC). Among these, seven (54%) had a global and diffuse staining pattern. Twelve of the C5b9+ patients also had deposition of C4d in GC and PTC. C4d deposits along GC and PTC were not associated with death-censored allograft survival (p = 0.42 and 0.69, respectively). However, death-censored allograft survival was significantly lower in patients with global and diffuse deposition of C5b9 in GC than those with a segmental pattern or no deposition (median survival after ABMR diagnosis, 6 months, 40.5 months and 44 months, respectively; p = 0.015). Double contour of glomerular basement membrane was diagnosed earlier after transplantation in C5b9+ ABMR than in C5b9– ABMR (median time after transplantation, 28 vs. 85 months; p = 0.058). In conclusion, we identified a new pattern of C5b9+ ABMR, associated with early onset of glomerular basement membrane duplication and poor allograft survival. Complement inhibitors might be a therapeutic option for this subgroup of patients

Le syndrome métabolique après transplantation rénale

MONTPELLIER-BU Médecine UPM (341722108) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Qualité du greffon et risque cardiovasculaire en transplantation rénale (influence de la présence d'athérome chez le donneur)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Retour en dialyse après échec de transplantation : comment améliorer les résultats dans cette population fragile ?

International audienceTen to 15 % of transplant recipients will return to dialysis, or require another transplantation within 5years, rising to 23 % by 10years, and failed transplantation is now one of the major indications for starting dialysis, accounting for almost 5 % of incident dialysis patients in the US and 10 % in France. Patients who resume dialysis post-transplantation have usually experienced an extended period of uraemia and long-term immunosuppressive therapy, and exhibit high rates of anaemia and erythropoietin resistance, hypoalbuminaemia and persistent chronic inflammation from the failed graft. These factors may increase mortality risk during the first year of dialysis, as observed in the US, but not in Canada or France. When compared to a control group of transplant-naive patients followed in the same institution in France, patients with transplant failure have a higher rate of usable arteriovenous fistula or graft, a similar rate of non-planned dialysis, and initiate dialysis with a higher glomerular filtration rate. We suggest that patient survival in dialysis after graft loss is influenced by both patient characteristics and quality of care, and this may explain the favourable outcome of this specific dialysis population in France

Prevalence and Risk Factors of Noncontrolled and Resistant Arterial Hypertension in Renal Transplant Recipients

International audienceBACKGROUND:Arterial hypertension (HT) is common in renal transplant recipients (RTRs). Control of HT is not optimal in this high-risk population despite recommendations for target blood pressure levels under 130/80 mm Hg.METHODS:We performed a cross-sectional analysis of the prevalence of uncontrolled HT, and using a Cox regression model, we identified the risk factors associated with resistant HT.RESULTS:Eight hundred eleven RTRs (>1 year after transplantation) were included. A total of 10.5% were normotensive (<130/80 mm Hg without treatment), 41% had controlled HT, 32.5% uncontrolled HT, and 16% resistant HT. In univariate analysis, compared to controlled HT, the RH group had significantly higher body mass index and older donors, delayed graft function, prevalence of metabolic syndrome (69.2 vs. 51.9%), fast glycemia and glycated hemoglobin, albuminuria, triglycerides and uric acid levels, and worse measured glomerular filtration rate (mGFR). In multivariate analysis, recipient age (P < 0,001), mGFR (P = 0.037), albuminuria (P < 0.001), and metabolic syndrome (P = 0.007) were significantly associated with RH. Association of metabolic syndrome with RH was much stronger than each of its components.CONCLUSION:Our data show that despite the recommendations issued by scientific societies, blood pressure control in RTRs is far from the recommended targets. At least a third of our patients (uncontrolled HT) did not receive optimal treatment and suffered therapeutic inertia. Decreased mGFR, metabolic syndrome, and urinary albumin excretion emerged as strong predictors of poor HT control. Whether prevention and management of the metabolic syndrome and reduction of albuminuria could help to more consistently reach the blood pressure recommended targets deserves further investigation

“Neuro‐renal syndrome” related to anti‐contactin‐1 antibodies

International audienc

Measuring intradialyser transmembrane and hydrostatic pressures: pitfalls and relevance in haemodialysis and haemodiafiltration

International audienceBackground Post-dilutional haemodiafiltration (HDF) with high convection volumes (HCVs) could improve survival. HCV-HDF requires a significant pressure to be applied to the dialyser membrane. The aim of this study was to assess the pressure applied to the dialysers in HCV-HDF, evaluate the influence of transmembrane pressure (TMP) calculation methods on TMP values and check how they relate to the safety limits proposed by guidelines. Methods Nine stable dialysis patients were treated with post-dilutional HCV-HDF with three different convection volumes [including haemodialysis (HD)]. The pressures at blood inlet (Bi), blood outlet (Bo) and dialysate outlet (Do) were continuously recorded. TMP was calculated using two pressures (TMP2: Bo, Do) or three pressures (TMP3: Bo, Do, Bi). Dialysis parameters were analysed at the start of the session and at the end of treatment or at the first occurrence of a manual intervention to decrease convection due to TMP alarms. Results During HD sessions, TMP2 and TMP3 remained stable. During HCV-HDF, TMP2 remained stable while TMP3 clearly increased. For the same condition, TMP3 could be 3-fold greater than TMP2. This shows that the TMP limit of 300 mmHg as recommended by guidelines could have different effects according to the TMP calculation method. In HCV-HDF, the pressure at the Bi increased over time and exceeded the safety limits of 600 mmHg provided by the manufacturer, even when respecting TMP safety limits. Conclusions This study draws our attention to the dangers of using a two-pressure points TMP calculation, particularly when performing HCV-HDF

Analyse de la validité du contenu et de la qualité formelle des questions isolées des épreuves classantes nationales informatisées (ECNi) de l’année universitaire 2015–2016

Contexte : Les premières épreuves classantes nationales informatisées (ECNi) clôturant le deuxième cycle des études médicales en France ont eu lieu en juin 2016 et ont comporté des dossiers cliniques progressifs (DCP), des questions isolées (QI), ainsi qu’une épreuve de lecture critique d’articles (LCA). Les QI représentaient une nouveauté de cet examen puisque les DCP et la LCA étaient utilisés depuis 2004. But : Analyse de la validité du contenu et de la qualité formelle des QI des premières épreuves ECNi. Méthodes : Un questionnaire contenant les critères docimologiques à recueillir a été défini et validé au préalable. Les 120 QI de l’ECNi 2016 ont été analysées par un binôme indépendant. Les discordances entre les évaluateurs ont été interprétées. Toutes les analyses ont été colligées sur tableur Excel puis les statistiques ont été réalisées sur Graphpad Prism version 6 et Stata v12. Résultats : Les rédacteurs des QI ont majoritairement respecté les consignes de forme. Les niveaux d’habiletés intellectuelles requis concernaient majoritairement les processus de mémorisation, de simple récupération de l’information et de compréhension (82 % des QI). Dans 7 à 23 % des QI, l’utilisation de distracteurs était jugée inappropriée. Une prédominance de QI portait sur les disciplines médicales (72,5 %). L’unité d’enseignement (« Circulation – Métabolismes ») était la plus représentée (26 %). Les discordances étaient faibles (6,2 % des évaluations). Conclusion : Il s’agit de la première analyse de la validité du contenu et de la qualité formelle des QI des ECNi. Leur format de rédaction a été largement respecté par les auteurs. Elles ont peu fait appel à des processus de raisonnement complexe. Il semblerait utile de favoriser les courtes vignettes cliniques pour améliorer cet aspect

Consequences of increasing convection onto patient care and protein removal in hemodialysis.

INTRODUCTION:Recent randomised controlled trials suggest that on-line hemodiafiltration (OL-HDF) improves survival, provided that it reaches high convective volumes. However, there is scant information on the feasibility and the consequences of modifying convection volumes in clinics. METHODS:Twelve stable dialysis patients were treated with high-flux 1.8 m2 polysulphone dialyzers and 4 levels of convection flows (QUF) based on GKD-UF monitoring of the system, for 1 week each. The consequences on dialysis delivery (transmembrane pressure (TMP), number of alarms, % of achieved prescribed convection) and efficacy (mass removal of low and high molecular weight compounds) were analysed. RESULTS:TMP increased exponentially with QUF (p56,000 monitoring values). Beyond 21 L/session, this resulted into frequent TMP alarms requiring nursing staff interventions (mean ± SEM: 10.3 ± 2.2 alarms per session, p 20L) is feasible by setting an HDF system at its optimal conditions based upon the GKD-UF monitoring. Prescribing higher convection volumes resulted in instability of the system, provoked alarms, was bothersome for the nursing staff and the patients, rarely achieved the prescribed convection volumes and increased removal of high molecular weight compounds, notably albumin

Successful treatment of a Streptococcus pneumoniae- associated haemolytic uraemic syndrome by eculizumab

International audienceHaemolytic uraemic syndrome (HUS) is a rare complication of invasive infection by Streptococcus pneumoniae (SP-HUS), especially in adults. Here we report an unusual case of a 53-year-old man presenting SP-HUS with severe multivisceral involvement. After failure of supportive care and plasma exchanges, eculizumab (anti-C5 antibody) resulted in a favourable outcome