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Le Touquet – Paris-Plage, France

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.


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.


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 de Nephrologie et Dialyses | Courbebaisse M.,University Pierre and Marie Curie | Souberbielle J.-C.,Service dExplorations Fonctionnelles | Souberbielle J.-C.,University of Paris Descartes | And 3 more authors.
Medecine/Sciences | Year: 2010

Vitamin D cannot any more be considered as exclusively necessary to prevent rickets or osteomalacia. Calcitriol produced in the kidney is known to have classical endocrine phosphocalcic properties. However, many other tissues express both vitamin D receptor and lα-hydroxylase and can convert 25-hydroxy vitamin D into calcitriol. Calcitriol produced locally is considered to have autocrine and paracrine actions on cellular proliferation and differentiation, apoptosis, insulin and renin secretion, interleukin and bactericidal proteins production. Epidemiologic and experimental data argue in favour of a protective role of vitamin D against cancers, type 2 diabetes, cardiovascular, auto-immune and infectious diseases, chronic kidney disease and loss of muscular strength. A few interventional studies confirm the protective effect of vitamin D against cancers, intermediate markers of cardiovascular risk, epidemic influenza, albuminuria and risk of fall. We present here the non phosphocalcic actions of vitamin D.


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.

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