Évaluation métabolique de patients transplantés rénaux en surpoids (effets d'un sevrage précoce en corticoïdes)

Les traitements immunosuppresseurs en greffe rénale ont des effets secondaires métaboliques. Notre étude évaluera, dans le sous-groupe des patients en surpoids, l effet d un sevrage précoce en corticoïdes sur la survenue de diabète post-transplantation et sur le contrôle d autres paramètres métaboliques. Matériels et Méthodes : c est une étude rétrospective, menée chez des greffés rénaux en surpoids, qui compare à six mois de greffe une cohorte sevrée à trois mois de corticoïdes (groupe M3) et une cohorte sevrée à trois jours de corticoïdes (groupe J3). Les critères sont la survenue d un diabète post-transplantation, la prise de poids, le bilan lipidique, la tension artérielle, la fonction rénale. Résultats : Chaque groupe comporte 19 patients. L IMC moyen est de 27.7 +/-2 kg/m dans le groupe M3 et de 27.5 +/- 5 kg/m dans le groupe J3 (p=0.25). La prévalence de diabète est de 21 % dans le groupe M3 et de 16% dans le groupe J3 (p=1). La prise de poids est de 2.6 +/- 3.9 kg dans le groupe M3 et de 0 +/- 4 kg dans le groupe J3 (p=0.03). Les tensions artérielles systolique et diastolique sont respectivement 133 +/- 13 mm Hg et 78 +/- 11 dans le groupe M3 et 145 +/- 18 mm Hg et 84 +/- 8 mm Hg dans le groupe J3. Les valeurs respectives de LDL et de triglycérides sont de 1.03 +/- 0.32 G.L et de 1.37 +/- 0.56 G.L dans le groupe M3 versus 1.07 +/- 0.42 G.l et 1.20 +/- 0.64 G.L dans le groupe J3. La clairance de la créatinine est de 53 +/- 15 mL/min dans le groupe M3 versus 56 +/- 14 mL/min dans le groupe J3 (p=0.46). Discussion : cette étude ne retrouve pas de bénéfice à un sevrage précoce en corticoïdes chez les transplantés rénaux en surpoids.GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort

Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13–431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/− 13 months. OPIs developed in 42(9.3%) patients after 14 +/− 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%; p < 0.001; and 11.6% vs. 2.4%, p < 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person–years. Incidence of CMV disease was 2.8/100 person–years, of pneumocystis pneumonia 1.6/100 person–years, and of aspergillosis 0.2/100 person–years. Multivariate analyses showed that estimated glomerular filtration (eGFR) < 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 − 10.3), p < 0.001). The incidence of EBV DNAemia was 17.3 events /100 person–years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/− 18 mL/min/1.73 m2 to 42.2 +/− 18 mL/min/1.73 m2 (p < 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk

Profiling Sirolimus-Induced Inflammatory Syndrome: A Prospective Tricentric Observational Study

<div><h3>Background</h3><p>The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive.</p> <h3>Methods</h3><p>30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch.</p> <h3>Results</h3><p>66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model.</p> <h3>Conclusions</h3><p>Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.</p> </div

Changes in concomitant immunosuppressive drugs after sirolimus introduction.

<p>Results are expressed in number of patients (%).</p

Summary of the data available for analysis.

<p>A) Mean ± SEM of sirolimus trough levels are indicated at each time points for CYP3A5 expressors and non-expressors. Dashed lines indicate the target values. B) Flowchart of SIRILYGRE study summarizing data available for analysis. Among the 4 patients (Pt) excluded because of sirolimus discontinuation, 2 (#25 & #27, in bold) experienced severe inflammatory symptoms. Five sera were excluded from analysis because of the presence of a documented confounding inflammatory condition (sepsis). For one patient (#11) no analysis of cytokine dosage could be performed because time point of collection was not indicated on the tubes.</p

Evolution of inflammatory cytokine levels correlates with clinical and biological manifestations of sirolimus-induced inflammatory syndrome.

<p>Pairwise correlation analysis was performed to determine how the changes of inflammatory cytokine levels are related to each other and with the changes of biological and clinical manifestations of sirolimus-induced inflammatory syndrome. The lower left half of the matrix is the color map of correlations. Bright colors indicate the pairs of variables closely correlated in the linear regression model (red for positive and blue for negative correlation). Faded colours encode for decreasing r values. The upper right half of the matrix is the colour map of p values. Decreasing p values are encoded from dark gray to dark green.</p

Biological changes associated with sirolimus introduction.

<p>Results are expressed as mean ± SD.*Estimated glomerular filtration rate (MDRD formula).</p