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Description phénotypique et exploration génétique d'une famille atteinte d'une hyalinose segmentaire et focale due à une mutation d'INF 2
Authors: --- --- ---
Year: 2016 Publisher: Bruxelles: UCL. Faculté de médecine et de médecine dentaire,

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Focal segmental glomerulosleroris (FSGS) is a chronic glomerular disease responsible for a glomerular syndrome (proteinuria, hypertension, microhematuria) and defined by a distinct microscopial pattern of glomerular sclerosis. Two seminal articles in 2010 and 2011 have shown that mutations in the INF2 (inverted formin2) gene cause an autosomal dominant form of FSGS, associated in a number of cases with Charcot Marie Tooth neuropathy. INF2 regulates the creation of actin filaments in podocytes and Schwann cells. Pathogenic INF2 mutations disrupt the actin cytoskeleton inside of these cells and lead to neurological and nephrological symptoms. Since 2010, only a small number of affected families have been described: the clinical presentation, the evolution, and the reasons behind large differences in the age of onset and progression of the disease have yet to be completely understood. This motivated me to study the medical records of several patients carrying on identical INF2 mutation, all belonging to a large Italian family. I have analyzed their clinical and biological data, their evolution, and I have looked for factors that correlate with the progression of the disease. Among 21 patients, the clinical presentation is marked by initial and progressive proteinuria, hypertension, and renal failure invariably progressing towards end stage renal disease. Microhematuria and oedemia are very rare. Median age of onset is 30, and median age of arrival in dialysis is 39. Large differences in the age at disease onset and at arrival in end-stage renal disease were prevalent in this family. No new symptom was identified, and none of the patients presented with symptoms of CMT neuropathy. In this group of patients, no new factor could be correlated with disease progression. In conclusion, in a large group of related patients, a pathogenic INF2 mutation lead to a proteinuric and hypertensive glomerulopathy, beginning in young adulthood and progressing invariably towards dialysis. Although no new factor could be shown to influence prognosis in this family, similar studies performed on a much larger cohort of patients could yield interesting results. L'hyalinose segmentaire et focale (HSF) est une maladie glomérulaire chronique causant un syndrome glomérulaire (protéinurie, hypertension, microhématurie) et caractérisée par une forme de destruction glomérulaire précise en microscopie optique. Aux Etats-Unis, chaque année, 25 000 personnes arrivent en dialyse à cause des conséquences de la maladie. Deux articles séminaux en 2010 et 2011 ont montré que des mutations dans le gène INF2 (inverted formin 2) causaient une variante autosomique dominante d'HSF, associée dans certains cas à 1 neuropathie de Charcot Marie Tooth (CMT). INF2 régule la formation des filaments l'actine dans les podocytes et les cellules de Schwann. Les mutations pathogènes d'INF2 perturbent le cytosquelette d'actine dans ces cellules et mènent aux signes cliniques. Depuis 2010, seules quelques familles de malades ayant ces mutations ont été étudiées dans le monde : le tableau clinique, l'évolution, et les raisons de différences majeures dans la sévérité de la maladie restent à préciser. Cela m'a poussé à étudier les dossiers médicaux de plusieurs patients avec une même nutation d'INF2 issus d'une grande famille italienne. J'ai analysé les données biologiques et cliniques, et leur évolution temporelle, et j'ai recherché des facteurs pouvant être corrélés avec l'âge de déclenchement de la maladie. Parmi les 21 malades étudiés, le tableau clinique est marqué par une triade récurrente : une protéinurie initiale et progressive, une hypertension artérielle, et une 1suffisance rénale chronique évoluant toujours vers le stade terminal. La microhématurie et les œdèmes sont généralement absents. L'âge médian de début les symptômes est de 30 ans, et l'âge médian d'arrivée en dialyse est de 39 ans. D'importantes différences dans les âges de découverte et d'arrivée en dialyse sont présentes dans cette famille. Aucun nouveau symptôme n'est retrouvé parmi ces malades, et aucun ne présente de signes de neuropathie de Charcot Marie Tooth. Aucun nouveau facteur pronostique n'a été identifié. En conclusion, les mutations d'INF2 causent un tableau de glomérulopathie protéinurique et hypertensive, débutant chez l'adulte jeune et évoluant vers la dialyse 'n quelques années. Malgré qu'aucun nouveau facteur pronostic n'ait pu être identifié dans cette famille, la recherche de corrélations pronostiques sur de plus grand nombre de malades pourrait produire des résultats intéressants.


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Kidney Inflammation, Injury and Regeneration
Authors: --- ---
ISBN: 3039285394 3039285386 Year: 2020 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of subsequent chronic kidney disease. Although the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function is urgently needed. The Special Issue covers research articles that investigated the molecular mechanisms of inflammation and injury during different renal pathologies, renal regeneration, diagnostics using new biomarkers, and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models. The Special Issue contains important reviews that consider the current knowledge of cell death and regeneration, inflammation, and the molecular mechanisms of kidney diseases. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells or their derivates is summarized. This edition is complemented by reviews that deal with the current data situation on other specific topics like diabetes and diabetic nephropathy or new therapeutic targets.

Keywords

microRNAs --- n/a --- transcription --- ischemia/reperfusion injury --- DSS-colitis --- kidney inflammation --- therapeutics targets --- CXCL13 --- glomerulus --- interleukin-6 --- rhabdomyolysis --- IgA nephropathy --- CREB Regulated Transcriptional Coactivators (CRTC) --- slit diaphragm --- injury --- xanthine oxidase --- Salt Inducible Kinase (SIK) --- acute and chronic kidney disease --- therapeutic target --- KIT-IgA score --- G-protein-coupled bile acid receptor (TGR5) --- lysophosphatidic acid --- glomerular injury --- IL-18 --- mesenchymal stem cells --- Taiwan --- acute kidney injury --- renal ischemia-reperfusion --- long non-coding RNA --- fibrosis --- acute kidney failure --- diabetic kidney diseases --- chronic kidney disease --- lncRNA --- LPS-binding protein --- endotoxemia-induced oliguric kidney injury --- dapagliflozin --- cPLA2 and COX-2 --- NLRP3 inflammasome --- CmklR1 --- haem --- chronic kidney injury --- omega-3 fatty acid --- noninvasive --- inflammation --- regulated necrosis --- GLP-1 receptor agonists --- miRNA --- AKI --- SGLT2 inhibitors --- diabetic kidney disease --- extracellular vesicles --- podocin --- type IV collagen --- epithelial cells --- nephrin --- 2-kidney-1-clip --- renal fibrosis --- papilla --- diagnostics --- necrosis --- non-coding RNAs --- podocyte --- Thy1.1 nephritis --- KIT assay --- oxidative stress --- conditioned medium --- C-reactive protein --- pericyte --- myofibroblast --- Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-?B) --- endotoxemia --- modifier gene --- polymorphism --- renal stem cells --- kidney --- polyploidization --- Class IIa Histone Deacetylases (HDAC) --- 2k1c --- molecular signaling --- proximal tubule --- arachidonic acid --- empagliflozin --- tubular injury --- signaling cascade --- signal transduction --- inflammatory maker --- niches --- biomarkers --- renal progenitors --- type V collagen --- cyclooxygenase --- focal segmental glomerulosclerosis --- inflammatory bowel disease (IBD) --- chronic kidney disease (CKD) --- allograft rejection --- renovascular hypertension --- genotype --- molecular mechanisms --- ROS --- prediction --- glomerular filtration barrier (GFB) --- alport syndrome --- scattered tubular cells --- long non-coding RNAs --- renal inflammation --- lysophosphatidic acid receptor --- cAMP Regulatory Element Binding Protein (CREB) --- Farnesiferol B --- differentiation --- mesenchymal stromal cells --- modified-MSCs --- kidney transplantation --- polyunsaturated fatty acids --- apoptosis --- type I collagen --- diabetes mellitus --- natural products --- lipoxygenase --- stem cell --- T cell-mediated rejection --- exosomes --- renal injury --- obese kidney fibrosis --- kidney injury --- cytotoxicity --- mesenchymal stem cell --- pigment nephropathy --- mesodermal stem cell --- ischemia-reperfusion --- cytochrome P450 --- renal cell carcinoma --- hematuria --- B-cell attracting chemokine --- microRNA --- chemerin --- glomerular basement membrane --- glomerular damage --- renal tubular cells --- kidney proximal tubule --- exosome --- hypertension --- diabetic nephropathy

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