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Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

Las estenosis del ureter son un problema frecuente en urologia. La diversidad de los tipos de estenosis, unicas o multiples, largas o cortas, intrinsecas o extrinsecas, refleja la variedad de las etiologias de estenosis ureterales (iatrogenicas, postirradiacion, traumaticas, infecciosas, extrinsecas, etc.). El diagnostico de una obstruccion es facil en caso de estenosis completa, pero puede ser mas dificil en caso de estenosis intermitente o parcial. En esta ultima situacion, es preferible limitar el numero de pruebas complementarias. El objetivo del tratamiento es evitar una perdida de nefronas y la atrofia renal. A la diversidad de las etiologias y de los tipos de estenosis ureterales responde la pluralidad de las tecnicas de tratamiento, desde la endoscopia hasta la cirugia abierta o laparoscopica. La eleccion de la tecnica depende de la evaluacion de las capacidades de recuperacion del rinon, de las caracteristicas de la estenosis, de la etiologia de la estenosis, de la experiencia del cirujano y de la operabilidad del paciente. Asi, a pesar de una tasa de exito claramente inferior a la de la cirugia, la endoscopia permitiria tratar las estenosis ureterales cortas con una menor morbilidad. Para la cirugia abierta o laparoscopica hay diversas tecnicas: reimplantacion ureteral, reemplazo ileal, autotrasplante o nefrectomia. Es preciso conocer bien la anatomia del ureter y en particular su vascularizacion. El principio de la anastomosis sin tension es prioritario para aumentar las posibilidades de exito de esta cirugia.

International audience; Cyst infection is a common complication of autosomal dominant polycystic kidney disease (ADPKD). Diagnosis is challenging with standard imaging techniques. We aimed to evaluate the diagnostic performance of [F-18] fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG PET-CT) for the diagnosis of cyst infections among ADPKD patients, in comparison with computed tomography (CT) and magnetic resonance imaging (MRI). All APKD patients who underwent 18-FDG PET-CT for suspected cyst infection between 2006 and 2013 in a French teaching hospital were included. Diagnosis of cyst infection was retained a posteriori on an index of clinical suspicion. 18-FDG PET-CT findings were was considered to be positive in cases of cyst wall hypermetabolism. CT or MRI findings were were considered to be positive in cases of cyst wall thickening (and enhancement if contrast medium was injected) and infiltration of the adjacent fat. A control group of ADPKD patients with 18-FDG PET-CT performed for other reasons was included. Thirty-two 18-FDG PET-CT scans were performed in 24 ADPKD patients with suspected cyst infection. A diagnosis of cyst infection was retained in 18 of 32 cases: 14 with positive 18-FDG PET-CT findings, and four false negatives. There were no false positives and no hypermetabolism of cyst walls in nine ADPKD control patients. 18-FDG PET-CT had a sensitivity of 77%, a specificity of 100%, and a negative predictive value of 77%. 18-FDG PET-CT allowed a differential diagnosis in three patients. In contrast, CT had a sensitivity of 7% and a negative predictive value of 35% (p < 0.001 vs. 18-FDG PET-CT). Only eight MRI scans were performed. The diagnostic performance of 18-FDG PET-CT is superior to that of CT in cyst infections, for comparable radiation doses and with no injection of nephrotoxic contrast medium, in ADPKD patients. (C) 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Objectifs L’endothelium allogenique du donneur constitue une interface entre le donneur et le receveur. Le vieillissement et les facteurs de risques cardiovasculaires presents dans le microenvironnement de ces transplants issus de donneurs marginaux contribuent a l’inflammation endotheliale et a la senescence vasculaire et peuvent avoir un effet deletere sur la reponse immunitaire du receveur ainsi que la fonction du greffon. Methodes La fraction vasculaire stromale (SVF) du tissu adipeux peri-renal (PRAT-SVF) preleve chez le donneur a ete isolee apres digestion enzymatique. Les cellules progenitrices endotheliales (ECFC) ont ete isolees par selection immuno-magnetique (CD144 + ) a partir de la PRAT-SVF prelevee chez 2 donneurs marginaux et 2 optimaux. Ces cellules ont ete amplifiees en culture. Le profil phenotypique et transcriptionnel des ECFC a ete etudie en cytometrie de flux et en qRT-PCR. Ces ECFC ont ete utilisees comme cibles pour evaluer l’activite endotheliotoxique d’anticorps circulants de receveurs presentant un rejet humoral, ainsi que l’effet pro-senescent des facteurs paracrines presents dans le liquide de perfusion de transplants marginaux. Resultats Ces travaux apportent une premiere preuve de faisabilite de l’isolement des cellules endotheliales de donneurs issues de PRAT-SVF. Ces cellules presentent un potentiel clonogenique d’expansion en culture ainsi qu’une expression des antigenes endotheliaux et HLA. Nous apportons ici la preuve que ces ECFC de SVF, amplifiees en culture, sont des cibles pertinentes permettant le depistage chez le receveur d’anticorps circulants anti-donneur et le monitoring d’anticorps anti-ABO lors de la desensibilisation humorale lors des transplantations ABO-incompatibles. Ces cellules endotheliales ont montre un profil inflammatoire et senescent accru en reponse a une stimulation par le liquide de perfusion de donneurs marginaux, montrant l’effet deletere du microenvironnement paracrine propre aux donneurs a criteres elargis. Conclusion Ce travail identifie une nouvelle strategie non invasive, qui utilise les ECFC issues de la PRAT-SVF comme un modele d’etude permettant d’indexer la reponse d’anticorps anti-endotheliaux en transplantation renale, et d’evaluer l’impact des facteurs paracrines qui caracterisent les donneurs marginaux sur la vulnerabilite vasculaire associee a la moindre survie de ces transplants.