Hôpital-Camfrout, France
Hôpital-Camfrout, France

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Buron F.,Service de Transplantation | Buron F.,University of Lyon | Malvezzi P.,Grenoble University Hospital Center | Villar E.,Departement Of Nephrologie Du Center Hospitalier Lyon Sud | And 21 more authors.
PLoS ONE | Year: 2013

Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2013 Buron et al.


Zuber J.,University of Paris Descartes | Grimbert P.,University Paris Est Creteil | Blancho G.,Nantes University Hospital Center | Thaunat O.,Service de Transplantation | And 3 more authors.
Nephrology Dialysis Transplantation | Year: 2013

A large body of evidence has been accumulated from experimental models in the past decade to support the critical role of Foxp3-expressing regulatory T cells (Tregs) in the suppression of alloimmune responses. This has prompted transplant clinicians to investigate whether Foxp3 analysis might be used as an immunodiagnostic tool for better assessment of the significance of graft infiltrate and to predict its impact on graft outcome. However, conflicting results have emerged from these studies and may have generated more confusion than clarification. Foxp3 expression has been antagonistically correlated with either good or poor prognosis. We discuss here how methodological issues and specific clinical settings may have accounted for the discrepancies between the results of these studies. Depending on many factors, including the techniques used, the method of sampling normalization, the extent of intra-graft inflammation, the immunosuppressive regimen and the depletion or repletion of T lymphocyte compartment, the significance of Foxp3 expression may vary. We propose here the conditions to be fulfilled in order to use Foxp3 analysis as a relevant biomarker for graft outcome assessment. Far from challenging the key role of Tregs in dampening alloimmune responses, this review highlights the need for technical harmonization and standards. © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


Conrad A.,Service de Transplantation | Brunet A.-S.,Service dHepatologie | Hervieu V.,Laboratoire danatomopathologie | Chauvet C.,Service de Transplantation | And 11 more authors.
Transplant Infectious Disease | Year: 2013

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature. © 2013 John Wiley & Sons A/S.


Calmus Y.,Unite de Transplantation Hepatique | Kamar N.,Service de Nephrologie | Gugenheim J.,Service du Pr Mouiel | Duvoux C.,Service de Chirurgie Digestive | And 11 more authors.
Transplantation | Year: 2010

Background. Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. Methods. This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 μmol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 μmmol/L at 6 months. Results. The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (≤100μmol/L or >100 μmol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 μmol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. CONCLUSIONS.: Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline. © 2010 by Lippincott Williams & Wilkins.


Thervet E.,University of Paris Descartes | Aouizerate J.,Service de Transplantation | Noel L.H.,Laboratoire dAnatomopathologie | Brocheriou I.,Service dAnatomopathologie | And 3 more authors.
Transplantation | Year: 2011

Background. Henoch-Schonlein Purpura nephropathy (HSPN) recurrence in renal transplant recipients (RTRs) has been reported in 35% of patients, leading in 11% of these patients to graft loss at 5 years. However, its true incidence is unknown. The aim of this study was to investigate this recurrence incidence using routine allograft biopsies (RBs). Methods. All RTRs with biopsy-proven HSP initial nephropathy were included (13 RTRs and 18 renal transplantations). At transplantation, the median age was 34 years, and 85% of RTRs were men. Overall, we analyzed 66 RBs that were routinely performed at 3 and 12 months after RT and when clinically indicated. Histologic recurrence was defined as the presence of IgA deposits within the mesangium and along the glomerular capillary walls. Results. After a median follow-up of 83 months (range, 13-232 months; interquartile range, 26-235 months), histologic recurrence was detected in 69% of patients and in 61% of grafts after a mean period of 24 months (range, 1-156 months). Clinical or biological signs were absent in all but one. Patient survival was 92.8%. Graft loss occurred in five cases, never were related to recurrence. At the last follow-up, the mean glomerular filtration rate was 48±14.2 mL/min/1.73 m; in patients with and without recurrence, the mean rates were 52.1±17.5 and 42.4±5.3 mL/min/1.73 m, respectively (P=0.27). Conclusion. Histologic recurrence of HSPN after RT is frequently observed on routine RBs but is not associated with clinical consequences. The short-term prognosis of recurrence is good, but its long-term prognosis remains to be determined. © 2011 by Lippincott Williams & Wilkins.


Foucher Y.,Nantes University Hospital Center | Foucher Y.,University of Nantes | Daguin P.,Nantes University Hospital Center | Daguin P.,University of Nantes | And 19 more authors.
Kidney International | Year: 2010

Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Données Informatisées et VAlidées en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver-operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world. © 2010 International Society of Nephrology.


Rogier T.,Service de medecine interne | Gerfaud-Valentin M.,Service de medecine interne | Pouteil-Noble C.,Service de transplantation | Taleb A.,Service de medecine interne | And 4 more authors.
Revue de Medecine Interne | Year: 2016

Introduction: Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest. Case report: A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900 mg per week 4 times, then 1200 mg every 2 weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7 intravenous injections. Conclusion: Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy. © 2016 Société nationale française de médecine interne (SNFMI).


PubMed | Service dhepato gastro enterologie et de nutrition clinique, Service de transplantation, Service de medecine interne and Service de reanimation medicale
Type: Journal Article | Journal: La Revue de medecine interne | Year: 2016

Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest.A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900mg per week 4times, then 1200mg every 2weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7intravenous injections.Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy.


PubMed | Service de Transplantation
Type: | Journal: Soins; la revue de reference infirmiere | Year: 2010

Renal transplantation is one of the possible substitution treatments for end-stage chronic renal failure. Nurses have an important part to play both before and after the transplant through their technical, interpersonal and educational role.


PubMed | Service de Transplantation
Type: Case Reports | Journal: Transplant infectious disease : an official journal of the Transplantation Society | Year: 2013

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were nave for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

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