The Experts below are selected from a list of 4965 Experts worldwide ranked by ideXlab platform
Samir K Gupta - One of the best experts on this subject based on the ideXlab platform.
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tenofovir associated Fanconi Syndrome review of the fda adverse event reporting system
Aids Patient Care and Stds, 2008Co-Authors: Samir K GuptaAbstract:ABSTRACT Tenofovir disoproxil fumarate (TDF) is a commonly used HIV antiretroviral. A relatively uncommon adverse effect of this drug is Fanconi Syndrome. What is known about this toxicity, especially in regards to concomitant medication use and outcomes, is limited to isolated case reports and small case series. Therefore, a retrospective review of the FDA Adverse Event Reporting System from 2001 through 2006 was conducted to examine demographics, concomitant medication use, outcomes, and temporal trends in reporting of Fanconi Syndrome associated with TDF use. In this large case series of 164 subjects who met the case definition for Fanconi Syndrome, the majority (83%) of the subjects received protease inhibitors (PI) with TDF; specifically, 74% of the total received a ritonavir-boosted PI. Didanosine was the most commonly (43%) prescribed nucleoside reverse transcriptase inhibitor (NRTI). The combination of didanosine with boosted PI was frequently observed (34%), and in particular, didanosine plus lop...
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tenofovir associated Fanconi Syndrome review of the fda adverse event reporting system
Aids Patient Care and Stds, 2008Co-Authors: Samir K GuptaAbstract:ABSTRACT Tenofovir disoproxil fumarate (TDF) is a commonly used HIV antiretroviral. A relatively uncommon adverse effect of this drug is Fanconi Syndrome. What is known about this toxicity, especially in regards to concomitant medication use and outcomes, is limited to isolated case reports and small case series. Therefore, a retrospective review of the FDA Adverse Event Reporting System from 2001 through 2006 was conducted to examine demographics, concomitant medication use, outcomes, and temporal trends in reporting of Fanconi Syndrome associated with TDF use. In this large case series of 164 subjects who met the case definition for Fanconi Syndrome, the majority (83%) of the subjects received protease inhibitors (PI) with TDF; specifically, 74% of the total received a ritonavir-boosted PI. Didanosine was the most commonly (43%) prescribed nucleoside reverse transcriptase inhibitor (NRTI). The combination of didanosine with boosted PI was frequently observed (34%), and in particular, didanosine plus lop...
Pierre J. Courtoy - One of the best experts on this subject based on the ideXlab platform.
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The renal Fanconi Syndrome in cystinosis: pathogenic insights and therapeutic perspectives
Nature Reviews Nephrology, 2017Co-Authors: Stephanie Cherqui, Pierre J. CourtoyAbstract:One of the first manifestations of cystinosis is a renal Fanconi Syndrome, characterized by severe dysfunction of proximal tubule cells. This Review describes the pathogenesis of renal Fanconi Syndrome in cystinosis, focusing on the importance of cystinosin in the maintenance of cellular homeostasis beyond its function in cystine transport. Cystinosis is a multi-systemic lysosomal storage disease caused by inactivating mutations in, or the absence of, the lysosomal membrane exporter for cystine, cystinosin; cystinosis is the main cause of hereditary renal Fanconi Syndrome Treatment with cysteamine efficiently depletes lysosomal cystine and delays progression to renal insufficiency; however, cysteamine does not reverse established renal Fanconi Syndrome, indicating functions of cystinosin beyond cystine transport Insights from mechanistic studies suggest that the pathological mechanisms of Fanconi Syndrome in cystinosis are multifactorial, involving oxidative stress and impaired vesicular trafficking, autophagy, and mTORC1 and TFEB signalling Haematopoietic stem cell (HSC) transplantation ameliorates renal Fanconi Syndrome in cystinotic mice; HSCs differentiate into macrophages that transfer cystinosin-bearing lysosomes into proximal tubule cells via tunnelling nanotubes that cross the tubular basement membrane Since tunnelling nanotubes contain donor-derived cytosol and carry all types of organelles, this mechanism should be generic and could be used to correct other genetic diseases that affect proximal tubule cells Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi Syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type. The current therapy for cystinosis, cysteamine, facilitates lysosomal cystine clearance and greatly delays progression to kidney failure but is unable to correct the Fanconi Syndrome. This Review summarizes decades of studies that have fostered a better understanding of the pathogenesis of the renal Fanconi Syndrome associated with cystinosis. These studies have unraveled some of the early molecular changes that occur before the onset of tubular atrophy and identified a role for cystinosin beyond cystine transport, in endolysosomal trafficking and proteolysis, lysosomal clearance, autophagy and the regulation of energy balance. These studies have also led to the identification of new potential therapeutic targets and here, we outline the potential role of stem cell therapy for cystinosis and provide insights into the mechanism of haematopoietic stem cell-mediated kidney protection.
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the renal Fanconi Syndrome in cystinosis pathogenic insights and therapeutic perspectives
Nature Reviews Nephrology, 2017Co-Authors: Stephanie Cherqui, Pierre J. CourtoyAbstract:Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi Syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type. The current therapy for cystinosis, cysteamine, facilitates lysosomal cystine clearance and greatly delays progression to kidney failure but is unable to correct the Fanconi Syndrome. This Review summarizes decades of studies that have fostered a better understanding of the pathogenesis of the renal Fanconi Syndrome associated with cystinosis. These studies have unraveled some of the early molecular changes that occur before the onset of tubular atrophy and identified a role for cystinosin beyond cystine transport, in endolysosomal trafficking and proteolysis, lysosomal clearance, autophagy and the regulation of energy balance. These studies have also led to the identification of new potential therapeutic targets and here, we outline the potential role of stem cell therapy for cystinosis and provide insights into the mechanism of haematopoietic stem cell-mediated kidney protection.
Pietro Andreone - One of the best experts on this subject based on the ideXlab platform.
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Tenofovir-induced Fanconi Syndrome in a patient with chronic hepatitis B monoinfection.
Annals of hepatology, 2016Co-Authors: Fabio Conti, Giovanni Vitale, Carmela Cursaro, Mauro Bernardi, Pietro AndreoneAbstract:Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor indicated for treatment of patients with chronic hepatitis B virus (CHB) and human immunodeficiency virus (HIV) infections. Despite the good safety profile of the drug, Fanconi Syndrome is a possible adverse reaction of TDF treatment, especially in HIV-infected patients. Only a few cases have been reported in patients with CHB-monoinfections. This report presents a case of a 58-year-old man with mild HBeAg-negative CHB who was exposed to TDF and developed drug-induced Fanconi Syndrome. Renal dysfunction reverted after TDF discontinuation and a switch to entecavir, and viral replication remained suppressed. A literature review yielded six additional cases of TDF-induced Fanconi Syndrome, all with risk factors for renal dysfunction despite the patients having normal glomerular filtration rates. We discuss the overall risk for Fanconi Syndrome in CHB-monoinfected patients exposed to TDF and the importance of careful monitoring of glomerular and tubular functions even when pre-existing kidney disease is not present.
P Lampertico - One of the best experts on this subject based on the ideXlab platform.
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tenofovir induced Fanconi Syndrome in chronic hepatitis b monoinfected patients that reverted after tenofovir withdrawal
Journal of Clinical Virology, 2014Co-Authors: M Vigano, Alessandra Brocchieri, A Spinetti, S Zaltron, G Mangia, F Facchetti, Alessandro Fugazza, Francesco Castelli, Massimo Colombo, P LamperticoAbstract:a b s t r a c t Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor widely used to treat patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi Syndrome have been reported among HIV patients exposed to TDF. In the HBV monoinfection scenario, only two cases of TDF-associated Fanconi Syndrome have been reported thus far. Here, we describe two additional patients with chronic hepatitis B (CHB) who developed a TDF-induced Fanconi Syndrome that reverted after TDF withdrawal and had viral replication fully suppressed upon switching to entecavir (ETV). Though the overall risk of TDF associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular function should be monitored in patients exposed to TDF, especially when other renal risk factors or a history of previous exposure to adefovir dipivoxil (ADV) are present.
Takashi Igarashi - One of the best experts on this subject based on the ideXlab platform.
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renal Fanconi Syndrome dent disease and bartter Syndrome
Genetics of Bone Biology and Skeletal Disease (Second Edition), 2017Co-Authors: Olivier Devuyst, Takashi IgarashiAbstract:Renal Fanconi Syndrome is characterized by a generalized dysfunction of the proximal renal tubule and a metabolic bone disease (rickets or osteomalacia). Renal Fanconi Syndrome is associated with various inherited tubulopathies and inborn errors of metabolism, immunological, or hematological disorders, and through exposure to various toxic agents. Dent disease (X-linked recessive nephrolithiasis, or X-linked recessive hypercalciuric hypophosphatemic rickets) is a renal tubular disorder caused by mutations in either the CLCN5 or OCRL genes. CLCN5 encodes the electrogenic Cl − /H + exchanger ClC-5, which is primarily located in the endosomes of the proximal tubule cells. The pathophysiology of the disease is essentially due to defective receptor-mediated endocytosis causing a generalized dysfunction of the cells. OCRL encodes a PIP2 5-phosphatase and mutations are also associated with the oculo–cerebro–renal Syndrome of Lowe, characterized by bilateral congenital cataract, severe mental retardation, and renal Fanconi Syndrome. The care of patients with Dent disease is supportive, focusing on the prevention of nephrolithiasis. The cautious use of thiazide diuretics has been suggested to treat the associated hypercalciuria.
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renal Fanconi Syndrome dent s disease and bartter s Syndrome
Devuyst Olivier; Igarashi Takashi (2012). Renal Fanconi syndrome dent's disease and bartter's syndrome. In: Thakker Rajesh V; Whyte Michael P; Eisman , 2013Co-Authors: Olivier Devuyst, Takashi IgarashiAbstract:Renal Fanconi Syndrome is characterized by a generalized dysfunction of the proximal renal tubule (PT) and a metabolic bone disease (rickets or osteomalacia). Renal Fanconi Syndrome is associated with various inborn errors of metabolism, immunological or hematological disorders, and through exposure to various toxic agents. Dent’s disease (X-linked recessive nephrolithiasis, or X-linked recessive hypercalciuric hypophosphatemic rickets) is a renal tubular disorder caused by mutations in either the CLCN5 or OCRL genes. CLCN5 encodes the electrogenic Cl − /H + exchanger ClC-5, which is primarily located in the endosomes of the PT cells. The pathophysiology of the disease is essentially due to defective receptor-mediated endocytosis causing a generalized dysfunction of PT cells. OCRL encodes a PIP 2 5-phosphatase and mutations are also associated with the oculo-cerebro-renal Syndrome of Lowe, characterized by bilateral congenital cataract, severe mental retardation, and renal Fanconi Syndrome. A few patients harboring CLCN5 mutations may present with a Bartter-like Syndrome, and some forms of Bartter Syndrome may be associated with hypercalciuria. The care of patients with Dent’s disease is supportive, focusing on the prevention of nephrolithiasis. The cautious use of thiazide diuretics has been suggested to treat the associated hypercalciuria.
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urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi Syndrome
Journal of The American Society of Nephrology, 2002Co-Authors: Anthony G W Norden, Catherine L Kelleher, Steven J Scheinman, Marta Lapsley, Hiroshi Shiraga, Takeshi Matsuyama, David P Sundin, Takashi Igarashi, Rajesh V Thakker, R J UnwinAbstract:Normal reabsorption of glomerular filtrate proteins probably requires recycling of the endocytic receptors megalin (gp330) and cubilin. Both receptors are located on the luminal surface of the renal proximal tubule epithelium. Whether abnormal amounts of receptor are present in the urine of patients with Dent's disease, Lowe's Syndrome, or autosomal dominant idiopathic Fanconi Syndrome was explored. They are all forms of the renal Fanconi Syndrome and are associated with tubular proteinuria. Urine samples of equal creatinine contents were dialyzed, lyophilized, and subjected to electrophoresis on nonreducing sodium dodecyl sulfate-5% polyacrylamide gels. Proteins were blotted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated protein. Megalin and cubilin levels detected by immunochemiluminescence were measured as integrated pixels and expressed as percentages of the normal mean values. A striking deficiency of urinary megalin, compared with normal individuals (n = 42), was observed for eight of nine families with Dent's disease (n = 10) and for the two families with Lowe's Syndrome (n = 3). The family with autosomal dominant idiopathic Fanconi Syndrome (n = 2) exhibited megalin levels within the normal range. The measured levels of cubilin were normal for all patients. These results are consistent with defective recycling of megalin to the apical cell surface of the proximal tubules and thus decreased loss into urine in Dent's disease and Lowe's Syndrome. This defect would interfere with the normal endocytic function of megalin, result in losses of potential ligands into the urine, and produce tubular proteinuria.
