Non-myeloma light chain cast nephropathy: a multicenter retrospective study on clinicopathological characteristics

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Étude descriptive du devenir et des modalités de prise en charge de l'insuffisance rénale chronique chez les sujets âgés de 70 ans et plus (à propos d'une cohorte rétrospective issue du Service de Néphrologie du CHU de Nantes)

Une augmentation de prévalence de la maladie rénale chronique (MRC) a été constatée en France et dans le Monde, en particulier chez les sujets âgés, qui ne bénéficient actuellement d'aucune recommandation spécifique de prise en charge. Notre étude monocentrique, rétrospective et observationnelle s'est intéressée aux modalités de prise en charge et aux devenirs de 807 patients âgés de 70 ans et plus et suivis dans le service de Néphrologie du CHU de Nantes pour une MRC définie par un débit de filtration glomérulaire estimé par la formule MDRD inférieur à 60 ml/min/1,73m2. Cent-quatre-vingt-seize patients (24,29%) ont atteint le stade de l'insuffisance rénale terminale (IRT) et 238 patients (29,49%) sont décédés au cours de la durée de suivi de l'étude estimée à 56,80 +- 30,71 mois. Six variables présentes à la date d'entrée dans l'étude ont été indépendamment associées au risque de survenue d'une IRT : un niveau de MDRD = 0,5 gr/24h, chaque baisse du taux d'hémoglobinémie d'1 g/dl, un nombre total de comorbidités associées à la MRC >= 3, un niveau de TAD >= 90 mmHg et l'absence de troubles du rythme cardiaque. Parmi les 196 patients ayant atteint le stade de l'IRT, un traitement de suppléance rénale a été débuté chez 107 patients (54,59%) (hémodialyse : n = 86 (43,88%), dialyse péritonéale : n = 13 (6,63%), greffe rénale : n = 10 (5,10%)), alors qu'un traitement conservateur a été décidé pour 35,20% d'entre-eux (n = 69). Les patients âgés de 80 ans et plus et aux antécédents de néoplasies à la date d'entrée dans l'étude présentaient un risque de choix de traitement conservateur multiplié par 4,7 (p =0,0001 et p = 0,0003, respectivement). Le type de traitement de l'IRT choisi est apparu comme un facteur de risque majeur influant sur la survie des patients en IRT, avec un risque de décès 6,89 fois plus important en cas de traitement conservateur comparativement aux patients en traitement de suppléance rénale (IC 95% = [3.57-13.27] ; p < 0,0001). Alors que la prise en charge des stades précoces de la MRC chez les sujets âgés semble bénéficier de recommandations proches de celles émises chez les adultes d'âge moyen pour en ralentir la progression et le risque d'IRT, celle de l'IRT, qui implique la décision de mise en place d'un traitement de suppléance rénale ou conservateur chez des sujets parfois très âgés, nécessite une évaluation plus globale pour proposer la meilleure stratégie en terme de survie mais aussi de qualité de vieNANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

L’analyse pharmacoprotéomique : application de l’analyse protéomique à la découverte et au développement de nouvelles thérapeutiques

L’analyse pharmacoprotéomique peut être définie comme étant l’analyse protéomique appliquée à la découverte de nouvelles cibles thérapeutiques ainsi qu’à l’étude des effets des médicaments. L’analyse protéomique permet d’appréhender les variations de l’expression protéique dans un système biologique en réponse à un stimulus ou en fonction d’un état physiologique ou physiopathologique donné. C’est donc une méthode de choix pour la découverte de nouvelles cibles thérapeutiques. C’est aussi une démarche intéressante dans l’étude du mode d’action et des effets biologiques des médicaments au cours de leur développement pré-clinique. Cette approche pharmacoprotéomique semble particulièrement intéressante pour la recherche de nouvelles altérations moléculaires impliquées dans la physiopathologie du diabète de type 2 et/ou de l’obésité ainsi que pour l’identification des mécanismes des traitements déjà existants ou à venir

Standardized and weighted time-dependent receiver operating characteristic curves to evaluate the intrinsic prognostic capacities of a marker by taking into account confounding factors

International audienceTime-dependent receiver operating characteristic curves allow to evaluate the capacity of a marker to discriminate between subjects who experience the event up to a given prognostic time from those who are free of this event. In this article, we propose an inverse probability weighting estimator of a standardized and weighted time-dependent receiver operating characteristic curve. This estimator provides a measure of the prognostic capacities by taking into account potential confounding factors. We illustrate the robustness of the estimator by a simulation-based study and its usefulness by two applications in kidney transplantation

PREventing Delayed Graft Function by Driving Immunosuppressive InduCtion Treatment (PREDICT-DGF): study protocol for a randomized controlled trial

International audienceBackground: In kidney transplantation, the use of Anti-Thymocyte Globulins (ATG) as induction therapy has been described as a possible treatment for reducing the prevalence of Delayed Graft Function (DGF). ATG possesses pharmaceutical proprieties that could help control the lesions caused by ischemia reperfusion injury. However, other studies have questioned this potential protective effeect. We hypothesized that the benefits related to ATG for reducing DGF prevalence may be higher and more consistently recognized if only patients with high DGF risk are considered. We recently proposed a scoring system entitled DGFS (Delayed Graft Function Score) for such stratification of kidney transplant recipients according to their risk of DGF. Using the DGFS calculation, we aim to determine whether a short course of ATG can decrease the incidence of DGF in comparison with Basiliximab in kidney transplant recipients with low immunological risk but high DGF risk.Methods: We conduct a phase IV, open label, randomized, multicentric and prospective study, to compare ATG in parallel with a control group treated by Basiliximab. The 1:1 randomized allocation of patients between groups is stratified on the clinical center, and on the hypothermic machine-perfusion device. We aimed to include a total of 384 patients to achieve a statistical power at 0.80. The study was initiated at the Nantes University hospital in July 2014, with data collection continuing until April 2018, and publication of the results proposed for 2019.Discussion: The main expected benefits of this study are i) the reduction of unjustified ATG over-prescriptions associated with serious adverse events, ii) the reduction of chance losses related to ATG under-prescription, iii) the decrease in the incidence of DGF which was described as a risk factor of graft failure and patient death, and iv) the reduction in hospitalization duration and number of post transplantation dialysis sessions, both being associated with reduced medical costs. In conclusion, the current study is innovative by proposing a more effeicient and personalized induction therapy

Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study

International audienceBackground and objectives. In contrast to the improvement in our understanding of the pathogenesis and presentation of autosomal recessive polycystic kidney disease (ARPKD), data regarding the issue of kidney and liver transplantation in patients with ARPKD remain particularly scarce. Here, we report the results and outcome of renal and/or liver transplantation in a series of patients with ARPKD. Methods. Fourteen ARPKD patients (age: 3-25 years) who underwent renal transplantation with or without liver transplantation were retrospectively identified in five French nephrology departments. The patients' medical charts were reviewed and relevant data were collected. Results. The clinical and radiological presentation of the 14 patients was highly variable illustrating the heterogeneity of ARPKD. Six patients underwent kidney and/or liver transplantation in adulthood. First renal graft survival was 92, 78 and 14% at 1, 5 and 10 years after renal transplantation, respectively. Mortality rate was relatively high (3/14; 21%) in these young patients and was directly related to infectious complications (recurrent angiocholitis) of severe Caroli's disease (dilatation of intra- and/or extra-hepatic bile ducts), a typical feature of ARPKD. Conclusions. Our data suggest that ARPKD patients evaluated for renal transplantation should be carefully screened for severe Caroli's disease. Even though the limited number of patients included in our study precludes any definite recommendation, pre-emptive liver transplantation may be a therapeutic option in ARPKD patients with severe Caroli's disease evaluated for renal transplantation

The Presence of Renal IgG Deposits in Necrotizing Crescentic Glomerulonephritis Associated with ANCA Is Not Related to Worse Renal Clinical Outcomes

International audienceIntroduction:Diagnosing the etiology of a rapidly progressive glomerulonephritis is of vital importance to guide appropriate therapeutic management. This case highlights the complexity involved in establishing diagnosis when presentation is atypical. In certain cases diagnosis cannot be established based on clinical presentation or biopsy findings alone, and critical analysis of biopsy findings in context of clinical presentation is crucial to guide the clinical decision-making process.Case presentation: A 47-year-old Hispanic male with history of granulomatosis with polyangiitis (GPA) in remission on azathioprine, presented with fatigue and lethargy. Physical examination was unremarkable. Laboratory data revealed elevated creatinine and otherwise normal electrolytes. Urinalysis showed numerous dysmorphic red blood cells with few red cell casts. His serologic results were all negative except anti-proteinase-3 antibody at very low titers. Kidney biopsy showed necrotizing crescentic glomerulonephritis with linear immunoglobulin G staining along the basement membrane.Conclusion: This case presented conflicting serologic and histopathologic findings. The presence of anti-proteinase-3 antibody supported diagnosis of recurrence of GPA. However, linear staining of immunoglobulin G (IgG) on immunofluorescence (IF) staining of renal biopsy supported anti-glomerular basement membrane (GBM) disease. The treatment of anti-GBM disease and GPA both involve immunosuppression with prednisone and cyclophosphamide. However, patients with anti-GBM disease are also treated with plasmapheresis early in the disease presentation to prevent further damage. The patient with GPA, on the other hand, was shown to benefit from plasmapheresis only in the case of severe renal disease (serum creatinine level more than 5 mg/dL) or pulmonary hemorrhage. In this case, since the patient did not have detectable circulating anti-GBM antibody, the decision was made not to proceed with plasmapheresis. The patient was treated with a standard immunosuppressive regimen consisting of prednisone and cyclophosphamide with partial renal recovery at 2 months

A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors

International audienceDelayed graft function (DGF) is a common complication in kidney transplantation and is known to be correlated with short-and long-term graft outcomes. Here we explored the possibility of developing a simple tool that could predict with good confidence the occurrence of DGF and could be helpful in current clinical practice. We built a score, tentatively called DGFS, from a French multicenter and prospective cohort of 1844 adult recipients of deceased donor kidneys collected since 2007, and computerized in the Données Informatisées et VAlidées en Transplantation databank. Only five explicative variables (cold ischemia time, donor age, donor serum creatinine, recipient body mass index, and induction therapy) contributed significantly to the DGF prediction. These were associated with a good predictive capacity (area under the ROC curve at 0.73). The DGFS calculation is facilitated by an application available on smartphones, tablets, or computers at www.divat.fr/en/online-calculators/ dgfs. The DGFS should allow the simple classification of patients according to their DGF risk at the time of transplantation, and thus allow tailored-specific management or therapeutic strategies