Service de Transplantation Renale

Paris, France

Service de Transplantation Renale

Paris, France
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Epaulard O.,Joseph Fourier University | Epaulard O.,French National Center for Scientific Research | Villier C.,Grenoble University Hospital Center | Ravaud P.,Service dEpidemiologie Clinique | And 10 more authors.
Clinical Infectious Diseases | Year: 2013

Background. Voriconazole long-term therapy is suspected to induce cutaneous squamous cell carcinoma (SCC), as suggested by 18 case reports worldwide and 3 retrospective studies.Methods. To better characterize the natural history of these potentially voriconazole-associated tumors, a nationwide call for notification of skin cancers and other skin lesions observed between 2002 and 2012 in patients treated by voriconazole was launched in France. A multidisciplinary committee evaluated voriconazole involvement in each case.Results. Nineteen SCCs were reported. The committee determined the likelihood of voriconazole involvement to be high in 15 cases, intermediate in 2, and low in 2. In the 17 patients with high/intermediate likelihood of voriconazole involvement, the mean time between voriconazole initiation and SCC diagnosis was 39 ± 18 months (range, 28-84 months), and was shorter in transplant recipients (35 vs 45 months, P <. 05). Cumulative mean duration of voriconazole therapy at SCC diagnosis was 35 months (range, 7-63 months). A multistep process was noted in 14 of 17 patients: acute phototoxicity during the first year of voriconazole therapy (mean time, 6 months [range, 0-18 months]), actinic keratosis (AK) of the same sun-exposed skin area in the second/third year (mean, 30 months [range, 11-57 months]), followed by SCC during the third year or later. Five cases of AK without SCC and 37 cases of other skin lesions were also reported.Conclusions. Our results suggest that long-term voriconazole prescription may be associated with a multistep phototoxic process involving acute skin lesions followed by AK then by SCC. Discontinuation of voriconazole should be strongly considered in patients experiencing chronic phototoxicity. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Sberro-Soussan R.,University of Paris Descartes | Zuber J.,University of Paris Descartes | Suberbielle-Boissel C.,Laboratoire dHistocompatibilite | Candon S.,University of Paris Descartes | And 13 more authors.
American Journal of Transplantation | Year: 2010

Persistence of donor-specific anti-HLA antibodies (DSA) associated with antibody-mediated graft injuries following kidney transplantation predicts evolution toward chronic humoral rejection and reduced graft survival. Targeting plasma cells, the main antibody-producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We evaluated the in vivo efficacy of one cycle of bortezomib (1.3 mg/m2 × 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing subacute antibody-mediated rejection with persisting DSA (>2000 [Mean Fluorescence Intensity] MFI). Bortezomib treatment did not significantly decrease DSA MFI within the 150-day posttreatment period in any patient. In addition, antivirus (HBV, VZV and HSV) antibody levels remained stable following treatment suggesting a lack of efficacy on long-lived plasma cells. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients in the time period studied. These results underscore the need to evaluate this new desensitization agent properly in prospective, randomized and well-controlled studies. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

PubMed | Service de Nephrologie et Dialyse, Limoges University Hospital Center, Angers University Hospital Center, Reims University Hospital Center and 6 more.
Type: Comparative Study | Journal: Transplant international : official journal of the European Society for Organ Transplantation | Year: 2016

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 27.3 ml/min vs. 47.8 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Giral M.,Nantes University Hospital Center | Foucher Y.,Nantes University Hospital Center | Foucher Y.,Institut Universitaire de France | Karam G.,Nantes University Hospital Center | And 11 more authors.
Journal of the American Society of Nephrology | Year: 2010

Long-term function of kidney allografts depends on multiple variables, one of which may be the compatibility in size between the graft and the recipient. Here, we assessed the long-term consequences of the ratio of the weight of the kidney to the weight of the recipient (KwRw ratio) in a multicenter cohort of 1189 patients who received a transplant between 1995 and 2006. The graft filtration rate increased by a mean of 5.74 ml/min between the third and sixth posttransplantation months among patients with a low KwRw ratio (<2.3 g/kg; P < 0.0001). In this low KwRw ratio group, the graft filtration rate remained stable between 6 months and 7 years but then decreased at a mean rate of 3.17 ml/min per yr (P < 0.0001). In addition, low KwRw ratios conferred greater risk for proteinuria, more antihypertensive drugs, and segmental or global glomerulosclerosis. Moreover, a KwRw ratio <2.3 g/kg associated with a 55% increased risk for transplant failure by 2 years of follow-up. In conclusion, incompatibility between graft and recipient weight is an independent predictor of long-term graft survival, suggesting that avoiding kidney and recipient weight incompatibility may improve late clinical outcome after kidney transplantation. Copyright © 2010 by the American Society of Nephrology.

Bienaime F.,University of Paris Descartes | Girard D.,Service de Biostatistique | Anglicheau D.,University of Paris Descartes | Canaud G.,University of Paris Descartes | And 8 more authors.
Journal of the American Society of Nephrology | Year: 2013

Kidney transplant recipients usually have low vitamin D levels, especially in the early posttransplantation period, but the association between vitamin D status with renal outcomes is not well described in this population. Here, we studied a prospective cohort of 634 kidney recipients who underwent transplantation at a single institution between January 2005 and June 2010. In this cohort, low 25-hydroxyvitamin D concentrations 3 months after transplantation did not predict early death or graft loss but were independently associated with lower measured GFR at 12 months (P=0.001) and higher risk for interstitial fibrosis and tubular atrophy (P=0.01). In contrast, levels of calcium, phosphorus, calcitriol, parathyroid hormone, or fibroblast growth factor-23 were not consistently associated with any of the studied outcomes. In conclusion, low 25-hydroxyvitamin D concentration measured 3 months after transplantation is an independent risk factor for interstitial fibrosis progression and is associated with a lower GFR 1 year after transplantation. Copyright © 2013 by the American Society of Nephrology.

Fougeray S.,French Institute of Health and Medical Research | Bouvier N.,French Institute of Health and Medical Research | Beaune P.,French Institute of Health and Medical Research | Legendre C.,Service de Transplantation Renale | And 3 more authors.
Cell Death and Disease | Year: 2011

The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote adaptive immunity. Interestingly, the UPR may activate inflammation pathways. Our aim was to test whether the UPR is activated during metabolic stress and mediates a tubular inflammatory response. Glucose deprivation, not hypoxia and amino acids deprivation, activated the UPR in humanrenal cortical tubular cells in culture. This stress activated NF-kB and promoted the transcription of proinflammatory cytokines and chemokines, including IL-6, IL-8, TNF-α, RANTES and MCP-1. The protein kinase RNA (PKR)-like ER kinase signaling pathway was not required for the induction of inflammation but amplified cytokine. Inositol-requiring enzyme 1 activated NF-kB signaling and was required for the transcription of proinflammatory cytokines and chemokines following metabolic stress. Moreover, acute ischemia activated ER stress and inflammation in rat kidneys. Finally, the ER stress marker GRP78 and NF-kB p65/RelA were coexpressed in human kidney transplants biopsies performed before implantation, suggesting that ER stress activates tubular inflammation in human renal allografts. In conclusion, this study establishes a link between ischemic stress, the activation of the UPR and the generation of a tubular inflammatory response. © 2011 Macmillan Publishers Limited All rights reserved.

Pereira H.,Service durologie | Buchler M.,Service de transplantation renale | Brichart N.,Service durologie | Haillot O.,Service durologie | And 4 more authors.
Progres en Urologie | Year: 2011

Objectives: To identify the risk factors for ureteral stenosis after renal transplantation and to evaluate their impact on both graft and patient survival. Patients and methods: This retrospective study included 789 kidney transplants among 782 patients performed at our institution between 1995 and 2007. The parameters studied included the characteristics of the donor, recipient and transplant, the surgical variables, the elements of the monitoring process and a graft and patient survival. Results: The ureteral stenosis rate after renal transplantation was found to be 6.5%, and the ureterovesical junction was the most common location (68%). A univariate analysis showed that this complication was significantly associated with a higher donor age (P = 0.01), abnormal graft revascularisation (P = 0.032) and DGF (Delay Graft Function) (P = 0.05). In multivariate analysis, only donor age (P = 0.001) and abnormal graft revascularisation (P = 0.035) were independent risk factors for ureteral stenosis after renal transplantation. When ureteral stenosis was treated, an analysis of the survival curves according to the Kaplan-Meier method did not reveal significant differences either in graft survival (P = 0.518) or overall survival of the patients (P = 0.614) as compared to the control group. Conclusions: In the present study, donor age and abnormal graft revascularisation were independent risk factors for ureteral stenosis after renal transplantation. This result is a strong argument for an ischemic component in the genesis of ureteral stenosis after renal transplantation, which should help to identify patients at risk. © 2010 Elsevier Masson SAS.

Courbebaisse M.,Service dExplorations Fonctionnelles | Courbebaisse M.,French Institute of Health and Medical Research | Courbebaisse M.,University of Paris Descartes | Diet C.,University of Paris Descartes | And 13 more authors.
American Journal of Nephrology | Year: 2012

Background: Cinacalcet decreases serum parathyroid hormone (PTH) and calcium concentrations in kidney transplant recipients with autonomous hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary calcium excretion and the risk of renal calcium deposits and may alter renal graft function. Methods: We studied 71 renal recipients with hypercalcemic hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3 and month 12 after renal transplantation. We compared phosphate calcium balance, measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet-treated and non-cinacalcet-treated patients. Measurements were performed before initiating cinacalcet treatment (month 3) and at month 12. Results: Patients treated with cinacalcet had more severe hyperparathyroidism. Serum PTH concentration decreased in both groups between months 3 and 12, but the decrease was much more important in cinacalcet-treated patients. Urinary calcium excretion significantly increased under cinacalcet treatment and was more than twice as high at month 12 as in patients who did not receive cinacalcet treatment. However, the hypercalciuria was not associated with an increase in calcium deposits on renal biopsies or an alteration of measured GFR. Conclusions: Despite sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet does not have adverse effects on GFR or on renal graft calcium deposits in the first year following renal transplantation. Copyright © 2012 S. Karger AG, Basel.

PubMed | Service de transplantation renale
Type: Journal Article | Journal: Nephrologie & therapeutique | Year: 2012

One of the most significant advances in medicine during the last 50 years is the development of organ transplantation. In the context of chronic kidney diseases, renal transplantation offers patients a better clinical outcome than other treatment options. However, the benefits of organ transplantation have not been maximized due to an inadequate supply of organs for transplantation. Despite the establishment of elaborate legal rules for organs procurement, both on deceased and living donors in numerous countries, ethical concerns remain. Most of them are consequences of the strategies implemented or proposed to address the so-called organ shortage. The involvement of society in these complex problems is crucial as numerous questions emerge: could actual state of organ procurement change? Is it possible and/or realistic to increase the number of organs, with respects to living donors or deceased persons? Is the shortage an indicator to limit the use of kidney transplantation? How do we maintain efficiency and justice, in this context.

Sberro-Soussan R.,Service de Transplantation Renale
Clinical transplants | Year: 2010

In a previous study we evaluated the in vivo efficacy of one cycle of Bortezomib (1.3 mg/m2 x 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing sub-acute antibody mediated rejection with persisting DSA. Bortezomib treatment did not significantly decrease DSA MFI within the 270-day posttreatment period in any patient. Here we reevaluate the patients' outcomes and bortezomib efficacy after one year post-treatment. The DSA levels remained stable or increased. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients.

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