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Xu-Dubois Y.-C.,French Institute of Health and Medical Research | Galichon P.,French Institute of Health and Medical Research | Brocheriou I.,Anatomo Pathologie | Brocheriou I.,University Pierre and Marie Curie | And 6 more authors.
Nephrology Dialysis Transplantation | Year: 2014

Background The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts. Methods We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication. Results We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ = 0.94, P < 0.0001; vimentin: ρ = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries. Conclusion This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss. © 2013 The Author. Source


Dubert M.,Urgences Nephrologiques et Transplantation Renale
BMJ case reports | Year: 2012

Antibiotics reduce the commensal flora in the gut, thereby facilitating the overgrowth of undesirable microorganisms such as Candida albicans. Here, we report the case of a 48-year-old woman with a history of obstructive uropathy consecutive to a radiation therapy, in whom both indwelling ureteral stents were rapidly occluded by fungal mycelia, resulting in a rapidly progressive kidney failure. Ascendant infection by C albicans had occurred after a 2- week course of antibiotics, prescribed for a perforative peritonitis also due to radiation-induced colitis. As shown by iterative CT scans made before (at the time of the diagnosis of peritonitis) and after the antibiotic course, kidney failure was explained by a sudden and bilateral pyelocaliceal dilation, due to the obstruction of the ureteral stents. Fungal mycelia were objectivised during the replacement procedure. Intravenous fluconazole was started, and renal function recovered ad integrum with the relief of the obstruction. Source


Tamouza H.,French Institute of Health and Medical Research | Tamouza H.,University Paris Diderot | Chemouny J.M.,French Institute of Health and Medical Research | Chemouny J.M.,University Paris Diderot | And 28 more authors.
Kidney International | Year: 2012

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. © 2012 International Society of Nephrology. Source


Kormann R.,Urgences Nephrologiques et Transplantation Renale | Languille E.,Urgences Nephrologiques et Transplantation Renale | Amiot H.-M.,Urgences Nephrologiques et Transplantation Renale | Hertig A.,Urgences Nephrologiques et Transplantation Renale | Hertig A.,University Pierre and Marie Curie
BMJ Case Reports | Year: 2012

We report the case of a 70-year-old woman who developed life-threatening arrhythmia as a result of acute and severe hypokalaemia, which she developed after consuming large quantities of a liquorice-rich herb tea. She had no previous heart condition. We also discuss the legislative discrepancy in both the USA and in Europe, whereby consumers are warned about the risk of chronic hypertension whenever they buy a product containing liquorice, yet the risk of hypokalaemia may not be mentioned at all. Copyright 2012 BMJ Publishing Group. All rights reserved. Source


Rafat C.,Urgences Nephrologiques et Transplantation Renale | Vimont S.,Service de microbiologie | Ancel P.Y.,APHP | Xu-Dubois Y.C.,Urgences Nephrologiques et Transplantation Renale | And 9 more authors.
Transplant Infectious Disease | Year: 2011

Background. Urinary tract infections (UTIs), the most common form of bacterial infection in kidney transplant recipients, recently have been demonstrated to be detrimental for long-term graft outcome. Therefore, reinforcing antibiotic prophylaxis might be vital, in addition to basic hygiene recommendations, surgical care, and prophylaxis by trimethoprim-sulfamethoxazole. Methods. In 2006, a Legionella pneumophila contamination of our department's water pipes meant that all the patients undergoing renal transplantation underwent a 1-month regimen of ofloxacin (OFLO) (200mg every other day). We took this opportunity to measure the incidence of UTI, including acute pyelonephritis (APN), in 100 consecutive patients transplanted before (n=50) and after (n=50) this treatment decision was reached. We also studied the antimicrobial resistance profiles in our department and in the rest of the hospital. Results. No patient developed Legionnaire's disease. A dramatic decrease in the incidence of UTI (-63%) was also seen in patients undergoing OFLO treatment. Logistic regression analysis demonstrated that the use of OFLO was independently associated with a reduction in UTI (odd ratio [OR]=0.31%, 95% confidence interval [CI] 0.11-0.84, P=0.02) and APN (OR=0.21%, 95% CI 0.07-0.98, P=0.045). This protection was sustained during the whole first year post transplantation. As for resistance rates, we observed a decrease in the susceptibility of Pseudomonas aeruginosa to ciprofloxacin in our nephrology department, compared with that observed in the rest of the hospital. The incidence of multi-resistant bacteria was stable. Discussion. Our unintentional extension of prophylactic antibiotherapy with OFLO gave rise to a dramatic decrease in the 1-year incidence of UTI and APN in kidney recipients. Emergence of resistant strains is, however, a major concern. © 2011 John Wiley & Sons A/S. Source

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