446 results on '"Torra, Roser'
Search Results
2. HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial
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Thomas Bais, Esther Meijer, Bart J. Kramers, Priya Vart, Marc Vervloet, Mahdi Salih, Bert Bammens, Nathalie Demoulin, Polina Todorova, Roman-Ulrich Müller, Jan Halbritter, Alexander Paliege, Emilie Cornec-Le Gall, Bertrand Knebelmann, Roser Torra, Albert C. M. Ong, Fiona E. Karet Frankl, and Ron T. Gansevoort
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Medicine (General) ,R5-920 - Abstract
Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD. Methods The HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care. Outcomes The primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume. Conclusion The HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.
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- 2024
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3. Clinical management of liver cyst infections: an international, modified Delphi-based clinical decision framework
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Duijzer, Renée, Bernts, Lucas H P, Geerts, Anja, van Hoek, Bart, Coenraad, Minneke J, Rovers, Chantal, Alvaro, Domenico, Kuijper, Ed J, Nevens, Frederik, Halbritter, Jan, Colmenero, Jordi, Kupcinskas, Juozas, Salih, Mahdi, Hogan, Marie C, Ronot, Maxime, Vilgrain, Valerie, Hanemaaijer, Nicolien M, Kamath, Patrick S, Strnad, Pavel, Taubert, Richard, Gansevoort, Ron T, Torra, Roser, Nadalin, Silvio, Suwabe, Tatsuya, Gevers, Tom J G, Cardinale, Vincenzo, Drenth, Joost P H, and Lantinga, Marten A
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- 2024
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4. Correlation of X chromosome inactivation with clinical presentation of Fabry disease in a case report
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Pablo Rodríguez Doyágüez, Mónica Furlano, Elisabet Ars Criach, Yolanda Arce, Lluís Guirado, and Roser Torra Balcells
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Fabry ,α-galactosidase A ,Globotriaosilceramida ,Lionización ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Fabry disease or also called Anderson-Fabry disease (FD) is a rare disease caused by pathogenic variants in the GLA gene, located on the X chromosome. This gene is involved in the metabolism of glycosphingolipids and its pathogenic variants cause a deficit or absence of α-galactosidase A causing the deposition of globotriaosylceramide throughout the body. Females have a variable phenotypic expression and a better prognosis than males. This is due to the X chromosome inactivation phenomenon. We present a clinical case of Fabry disease in a female with predominantly renal involvement and demonstrate how the X chromosome inactivation phenomenon is tissue dependent, showing preferential inactivation of the mutated allele at the renal level. Resumen: La enfermedad de Fabry o también llamada de Anderson-Fabry (EF) es una enfermedad rara, causada por variantes patogénicas en el gen GLA, localizado en el cromosoma X. Este gen interviene en el metabolismo de los glucoesfingolípidos y variantes patogénicas en el mismo causan déficit o ausencia de la α-galactosidasa A ocasionando el depósito de globotriaosilceramida en todo el organismo. Las mujeres presentan una expresión fenotípica variable y de mejor pronóstico que los varones. Esto es debido al fenómeno de inactivación del cromosoma X. Presentamos un caso clínico de enfermedad de Fabry en una mujer con afectación predominantemente renal y demostramos cómo el fenómeno de la inactivación del cromosoma X es tejido dependiente, mostrando una inactivación preferencial del alelo mutado a nivel renal.
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- 2023
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5. [Genetic study in young patients with chronic kidney disease stage G5 from unknown etiology. The GENSEN study design
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Blasco, Miquel, Quiroga, Borja, García-Aznar, José M., Torra, Roser, Ortiz, Alberto, and de Sequera, Patricia
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- 2024
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6. Reassuring pregnancy outcomes in women with mild COL4A3-5–related disease (Alport syndrome) and genetic type of disease can aid personalized counseling
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Gosselink, Margriet E., Snoek, Rozemarijn, Cerkauskaite-Kerpauskiene, Agne, van Bakel, Sophie P.J., Vollenberg, Renee, Groen, Henk, Cerkauskiene, Rimante, Miglinas, Marius, Attini, Rossella, Tory, Kálmán, Claes, Kathleen J., van Calsteren, Kristel, Servais, Aude, de Jong, Margriet F.C., Gillion, Valentine, Vogt, Liffert, Mastrangelo, Antonio, Furlano, Monica, Torra, Roser, Bramham, Kate, Wiles, Kate, Ralston, Elizabeth R., Hall, Matthew, Liu, Lisa, Hladunewich, Michelle A., Lely, A. Titia, and van Eerde, Albertien M.
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- 2024
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7. The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants
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Sánchez, Rosario, Ripoll-Vera, Tomás, López-Mendoza, Manuel, de Juan-Ribera, Joaquín, Gimeno, Juan Ramón, Hermida, Álvaro, Ruz-Zafra, María Aurora, Torregrosa, José Vicente, Mora, Antonia, García-Pinilla, José Manuel, Fortuny, Elena, Aguinaga-Barrilero, Ana, and Torra, Roser
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- 2023
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8. An Artificial Intelligence Generated Automated Algorithm to Measure Total Kidney Volume in ADPKD
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Taylor, Jonathan, Thomas, Richard, Metherall, Peter, van Gastel, Marieke, Cornec-Le Gall, Emilie, Caroli, Anna, Furlano, Monica, Demoulin, Nathalie, Devuyst, Olivier, Winterbottom, Jean, Torra, Roser, Perico, Norberto, Le Meur, Yannick, Schoenherr, Sebastian, Forer, Lukas, Gansevoort, Ron T., Simms, Roslyn J., and Ong, Albert C.M.
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- 2024
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9. Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease
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Fervenza, Fernando C, Torra, Roser, and Warnock, David G
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- 2008
10. A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene
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Gloria Fraga, M. Alba Herreros, Marc Pybus, Miriam Aza-Carmona, Melissa Pilco-Teran, Mónica Furlano, M. José García-Borau, Roser Torra, and Elisabet Ars
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X-linked hypophosphatemia ,PHEX gene ,non-canonical splice site variant ,Genetics ,QH426-470 - Abstract
X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the PHEX gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the PHEX gene. Segregation analysis detected that the consultand’s father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand’s son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the PHEX gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the PHEX gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of PHEX transcripts with aberrant and wild-type splicing.
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- 2024
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11. Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study
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Eugenia García Montemayor, Victoria, Salgueira Lazo, Mercedes, Mazuecos Blanca, Auxiliadora, Jiménez Salcedo, Tamara, José Espigares Huete, María, Araceli Jiménez Vibora, Elena, Álamo Caballero, Concepción, Banegas Deras, Eduardo J., Alonso Bethencourt, Alejandro, Rodríguez García, Alejandra, Fernández Granados, Saulo, Fernández Fresnedo, Gema, Calle García, Leonardo, Martín García, Jesús, Estifan Kasabji, Jorge, Jesús Izquierdo, María, Mouzo Mirco, Ricardo, García Agudo, Rebeca, de Arriba de la Fuente, Gabriel, Facundo Molas, Carme, Xipell Font, Marc, Yugueros González, Alejandra, Antóns, Paula, Ibernon Vilaro, Meritxell, de la Fuente Fernández, Vanessa, González Galván, Yussel, Cabezas, Antonio, Castro Alonso, Cristina, Juan García, Isabel, Garín Cascales, Eduardo, Sebastiá Morant, Josepa, Luna Complejo, Enrique, María Díaz Campillejo, Rosa, González Sanchidrián, Silvia, Cao Vilariño Complejo, Mercedes, Sierra Carpio, Milagros, Ortega Díaz, Mayra, Sánchez Hernández, Rosa, Ossorio González, Marta, Vega Martínez, Almudena, Teresa López Picasso, María, Goma, Elena, Giorgi, Martín, Martínez Miguel, Patricia, Gutiérrez Martínez, Eduardo, Paraíso Cuevas, Vicente, Echarri, Rocío, Martínez, Víctor, Pérez Arnedo, Mario, Juliana Castañeda Infante, Laura, Antonio Menacho Miguel, Jose, Blasco, Miquel, Quiroga, Borja, García-Aznar, José M., Castro-Alonso, Cristina, Fernández-Granados, Saulo J., Luna, Enrique, Ossorio, Marta, Izquierdo, María Jesús, Sanchez-Ospina, Didier, Castañeda-Infante, Laura, Mouzo, Ricardo, Cao, Mercedes, Besada-Cerecedo, María L., Pan-Lizcano, Ricardo, Torra, Roser, Ortiz, Alberto, and de Sequera, Patricia
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- 2024
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12. Correction: The 2019 and 2021 International workshops on Alport syndrome
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Daga, Sergio, Ding, Jie, Deltas, Constantinos, Savige, Judy, Lipska-Ziętkiewicz, Beata S., Hoefele, Julia, Flinter, Frances, Gale, Daniel P., Aksenova, Marina, Kai, Hirofumi, Perin, Laura, Barua, Moumita, Torra, Roser, Miner, Jeff H., Massella, Laura, Ljubanović, Danica Galešić, Lennon, Rachel, Weinstock, Andrè B., Knebelmann, Bertrand, Cerkauskaite, Agne, Gear, Susie, Gross, Oliver, Turner, A. Neil, Baldassarri, Margherita, Pinto, Anna Maria, and Renieri, Alessandra
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- 2024
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13. Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study
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Daniel G. Bichet, Robert J. Hopkin, Patrício Aguiar, Sridhar R. Allam, Yin-Hsiu Chien, Roberto Giugliani, Staci Kallish, Sabina Kineen, Olivier Lidove, Dau-Ming Niu, Iacopo Olivotto, Juan Politei, Paul Rakoski, Roser Torra, Camilla Tøndel, and Derralynn A. Hughes
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chaperone therapy ,alpha-galactosidase A ,globotriaosylsphingosine ,amenability ,treatment decisions ,patient journey ,Medicine (General) ,R5-920 - Abstract
ObjectiveFabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat.MethodsA modified Delphi process was conducted to determine consensus on treatment decisions and monitoring of patients with Fabry disease receiving migalastat. The multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease. Two rounds of Delphi surveys were completed and recommendations on the use of biomarkers, multidisciplinary monitoring, and treatment decisions were generated based on statements that reached consensus.ResultsThe expert panel reached consensus agreement on 49 of 54 statements, including 16 that reached consensus in round 1. Statements that reached consensus agreement are summarized in recommendations for migalastat treatment and monitoring, including baseline and follow-up assessments and frequency. All patients with Fabry disease and an amenable mutation may initiate migalastat treatment if they have evidence of Fabry-related symptoms and/or organ involvement. Treatment decisions should include holistic assessment of the patient, considering clinical symptoms and organ involvement as well as patient-reported outcomes and patient preference. The reliability of α-Gal A and globotriaosylsphingosine as pharmacodynamic response biomarkers remains unclear.ConclusionThese recommendations build on previously published guidelines to highlight the importance of holistic, multidisciplinary monitoring for patients with Fabry disease receiving migalastat, in addition to shared decision-making regarding treatments and monitoring throughout the patient journey.GRAPHICAL ABSTRACT
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- 2023
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14. The Spanish Fabry women study: a retrospective observational study describing the phenotype of females with GLA variants
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Rosario Sánchez, Tomás Ripoll-Vera, Manuel López-Mendoza, Joaquín de Juan-Ribera, Juan Ramón Gimeno, Álvaro Hermida, María Aurora Ruz-Zafra, José Vicente Torregrosa, Antonia Mora, José Manuel García-Pinilla, Elena Fortuny, Ana Aguinaga-Barrilero, and Roser Torra
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Fabry disease ,X-linked disorder ,GLA variants ,Females ,Organ involvement ,Medicine - Abstract
Abstract Background Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.
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- 2023
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15. The 2019 and 2021 International Workshops on Alport Syndrome
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Daga, Sergio, Ding, Jie, Deltas, Constantinos, Savige, Judy, Lipska-Ziętkiewicz, Beata S., Hoefele, Julia, Flinter, Frances, Gale, Daniel P., Aksenova, Marina, Kai, Hirofumi, Perin, Laura, Barua, Moumita, Torra, Roser, Miner, Jeff H., Massella, Laura, Ljubanović, Danica Galešić, Lennon, Rachel, Weinstock, Andrè B., Knebelmann, Bertrand, Cerkauskaite, Agne, Gear, Susie, Gross, Oliver, Turner, A. Neil, Baldassarri, Margherita, Pinto, Anna Maria, and Renieri, Alessandra
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- 2022
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16. Consensus document on autosomal dominant polycystic kindey disease from the Spanish Working Group on Inherited Kindey Diseases. Review 2020
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Elisabet Ars, Carmen Bernis, Gloria Fraga, Mónica Furlano, Víctor Martínez, Judith Martins, Alberto Ortiz, Maria Vanessa Pérez-Gómez, José Carlos Rodríguez-Pérez, Laia Sans, and Roser Torra
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PQRAD ,Poliquistosis renal autosómica dominante ,Recomendaciones ,Manejo ,Progresión ,Consenso ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent cause of genetic renal disease and accounts for 6–10% of patients on kidney replacement therapy (KRT).Very few prospective, randomized trials or clinical studies address the diagnosis and management of this relatively frequent disorder. No clinical guidelines are available to date. This is a revised consensus statement from the previous 2014 version, presenting the recommendations of the Spanish Working Group on Inherited Kidney Diseases, which were agreed to following a literature search and discussions. Levels of evidence mostly are C and D according to the Centre for Evidence-Based Medicine (University of Oxford). The recommendations relate to, among other topics, the use of imaging and genetic diagnosis, management of hypertension, pain, cyst infections and bleeding, extra-renal involvement including polycystic liver disease and cranial aneurysms, management of chronic kidney disease (CKD) and KRT and management of children with ADPKD. Recommendations on specific ADPKD therapies are provided as well as the recommendation to assess rapid progression. Resumen: La poliquístosis renal autosómica dominante (PQRAD) es la causa más frecuente de nefropatía genética y representa entre 6 a 10% de los pacientes en terapia de reemplazo renal (TRR).Muy pocos ensayos prospectivos, aleatorizados o estudios clínicos abordan el diagnóstico y el tratamiento de este trastorno relativamente frecuente. No hay guías clínicas disponibles hasta la fecha. Esta es un docuemento de consenso revisada de la versión anterior de 2014, que presenta las recomendaciones del Grupo de Trabajo Español de Enfermedades Renales Hereditarias, acordadas tras la búsqueda bibliográfica y discusiones. Los niveles de evidencia en su mayoría son C y D según el Centro de Medicina Basada en Evidencia (Universidad de Oxford). Las recomendaciones se relacionan, entre otros temas, con el uso de diagnóstico por imágenes y genético, el manejo de la hipertensión, el dolor, las infecciones y el sangrado quístico, la afectación extrarrenal, incluida la enfermedad poliquística hepática y los aneurismas craneales, el manejo de la enfermedad renal crónica (ERC) y el TRR asi como el seguimiento de niños con PQRAD. Se proporcionan recomendaciones sobre terapias específicas para la PQRAD, así como la recomendación para evaluar la rápida progresión.
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- 2022
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17. EASL Clinical Practice Guidelines on the management of cystic liver diseases
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Drenth, Joost, Barten, Thijs, Hartog, Hermien, Nevens, Frederik, Taubert, Richard, Torra Balcells, Roser, Vilgrain, Valerie, and Böttler, Tobias
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- 2022
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18. Consensus document on autosomal dominant polycystic kindey disease from the Spanish Working Group on Inherited Kindey Diseases. Review 2020
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Ars, Elisabet, Bernis, Carmen, Fraga, Gloria, Furlano, Mónica, Martínez, Víctor, Martins, Judith, Ortiz, Alberto, Pérez-Gómez, Maria Vanessa, Rodríguez-Pérez, José Carlos, Sans, Laia, and Torra, Roser
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- 2022
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19. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
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Köttgen, Anna, Cornec-Le Gall, Emilie, Halbritter, Jan, Kiryluk, Krzysztof, Mallett, Andrew J., Parekh, Rulan S., Rasouly, Hila Milo, Sampson, Matthew G., Tin, Adrienne, Antignac, Corinne, Ars, Elisabet, Bergmann, Carsten, Bleyer, Anthony J., Bockenhauer, Detlef, Devuyst, Olivier, Florez, Jose C., Fowler, Kevin J., Franceschini, Nora, Fukagawa, Masafumi, Gale, Daniel P., Gbadegesin, Rasheed A., Goldstein, David B., Grams, Morgan E., Greka, Anna, Gross, Oliver, Guay-Woodford, Lisa M., Harris, Peter C., Hoefele, Julia, Hung, Adriana M., Knoers, Nine V.A.M., Kopp, Jeffrey B., Kretzler, Matthias, Lanktree, Matthew B., Lipska-Ziętkiewicz, Beata S., Nicholls, Kathleen, Nozu, Kandai, Ojo, Akinlolu, Parsa, Afshin, Pattaro, Cristian, Pei, York, Pollak, Martin R., Rhee, Eugene P., Sanna-Cherchi, Simone, Savige, Judy, Sayer, John A., Scolari, Francesco, Sedor, John R., Sim, Xueling, Somlo, Stefan, Susztak, Katalin, Tayo, Bamidele O., Torra, Roser, van Eerde, Albertien M., Weinstock, André, Winkler, Cheryl A., Wuttke, Matthias, Zhang, Hong, King, Jennifer M., Cheung, Michael, Jadoul, Michel, Winkelmayer, Wolfgang C., and Gharavi, Ali G.
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- 2022
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20. Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?
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Hughes, Derralynn A., Aguiar, Patrício, Lidove, Olivier, Nicholls, Kathleen, Nowak, Albina, Thomas, Mark, Torra, Roser, Vujkovac, Bojan, West, Michael L., and Feriozzi, Sandro
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- 2022
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21. Do clinical guidelines facilitate or impede drivers of treatment in Fabry disease?
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Derralynn A. Hughes, Patrício Aguiar, Olivier Lidove, Kathleen Nicholls, Albina Nowak, Mark Thomas, Roser Torra, Bojan Vujkovac, Michael L. West, and Sandro Feriozzi
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Fabry disease ,Guideline ,Consensus ,Renal ,Cardiac ,Neurological ,Medicine - Abstract
Abstract Background Variable disease progression confounds accurate prognosis in Fabry disease. Evidence supports the long-term benefit of early intervention with disease-specific therapy, but current guidelines recommend treatment initiation based on signs that may present too late to avoid irreversible organ damage. Findings from the ‘PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease’ (PREDICT-FD) initiative included expert consensus on 27 early indicators of disease progression in Fabry disease and on drivers of and barriers to treatment initiation in Fabry disease. Here, we compared the PREDICT-FD indicators with guidance from the European Fabry Working Group and various national guidelines to identify differences in signs supporting treatment initiation and how guidelines themselves might affect initiation. Finally, anonymized patient histories were reviewed by PREDICT-FD experts to determine whether PREDICT-FD indicators supported earlier treatment than existing guidance. Results Current guidelines generally aligned with PREDICT-FD on indicators of renal involvement, but most lacked specificity regarding cardiac indicators. The prognostic significance of neurological indicators such as white matter lesions (excluded by PREDICT-FD) was questioned in some guidelines and excluded from most. Some PREDICT-FD patient-reported signs (e.g., febrile crises) did not feature elsewhere. Key drivers of treatment initiation in PREDICT-FD were: (A) male sex, young age, and clinical findings (e.g., severe pain, organ involvement), (B) improving clinical outcomes and preventing disease progression, and (C) a family history of Fabry disease (especially if outcomes were severe). All guidelines aligned with (A) and several advocated therapy for asymptomatic male patients. There was scant evidence of (B) in current guidance: for example, no countries mandated ancillary symptomatic therapy, and no guidance advocated familial screening with (C) when diagnosis was confirmed. Barriers were misdiagnosis and a lack of biomarkers to inform timing of treatment. Review of patient histories generally found equal or greater support for treatment initiation with PREDICT-FD indicators than with other guidelines and revealed that the same case and guideline criteria often yielded different treatment recommendations. Conclusions Wider adoption of PREDICT-FD indicators at a national level could promote earlier treatment in Fabry disease. Clearer, more concise guidance is needed to harmonize treatment initiation in Fabry disease internationally.
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- 2022
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22. Kidney health matters: a global imperative for public health.
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Torra, Roser
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MEDICAL personnel , *NEUROLOGICAL disorders , *LOW birth weight , *GLOBAL burden of disease , *KIDNEY failure , *NON-communicable diseases , *HEART failure - Abstract
A joint statement by the International Society of Nephrology, the European Renal Association, and the American Society of Nephrology is calling for kidney disease to be recognized as a major non-communicable disease (NCD) by the World Health Organization (WHO). Kidney disease has a high global prevalence and has been overlooked for too long, resulting in low awareness, inadequate resources, and limited access to care, particularly in low- and middle-income countries. The statement highlights the significant impact of kidney disease on public health, the environment, and healthcare systems, and emphasizes the need for action, prioritization, and investment in research and innovation. By including kidney disease on the global health agenda, lives can be saved, suffering can be reduced, and health equity can be promoted. [Extracted from the article]
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- 2024
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23. Increased prevalence of kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.
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Furlano, Mónica, Pilco-Teran, Melissa, Pybus, Marc, Martínez, Víctor, Aza-Carmona, Miriam, Peris, Asunción Rius, Pérez-Gomez, Vanessa, Berná, Gerson, Mazon, Jaime, Hernández, Jonathan, Arizón, Leonor Fayos de, Viera, Elizabet, Gich, Ignasi, Pérez, Hugo Vergara, Gomá-Garcés, Elena, Dolon, José Luis Albero, Ars, Elisabet, and Torra, Roser
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CYSTIC kidney disease ,RENAL replacement therapy ,GLOMERULAR filtration rate ,CHRONIC kidney failure ,PROTEINURIA - Abstract
Background Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3 / COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 -related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4 and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3 / COL4A4 genes is assessed in this study. Methods We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, estimated glomerular filtration rate (eGFR) and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. Results Half of the individuals with P/LP variants in COL4A3 / COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (P < .001). No association was found between KC and proteinuria, sex or causative gene. Conclusions Individuals with COL4A3 / COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy
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Marian Goicoechea, Francisco Gomez-Preciado, Silvia Benito, Joan Torras, Roser Torra, Ana Huerta, Alejandra Restrepo, Jessica Ugalde, Daniela Estefania Astudillo, Irene Agraz, Manuel Lopez-Mendoza, Gabriel de Arriba, Elena Corchete, Borja Quiroga, Maria Jose Gutierrez, Maria Luisa Martin-Conde, Vanessa Lopes, Carmela Ramos, Irene Mendez, Mercedes Cao, Fernando Dominguez, and Alberto Ortiz
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Enfermedad de Fabry ,Enfermedad renal crónica ,Tratamiento enzimático sustitutivo ,Eventos renales ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120). Results: In 69 patients (42 males, 27 females, mean age 44.6 ± 13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤ 60 ml/min/1.73 m2 (log Rank 12.423, p = 0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p = 0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. Resumen: El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo. Diseño del estudio: Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico. Resultados: Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6 ± 13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128 mg/g (p = 0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe
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- 2021
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25. Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy
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Goicoechea, Marian, Gomez-Preciado, Francisco, Benito, Silvia, Torras, Joan, Torra, Roser, Huerta, Ana, Restrepo, Alejandra, Ugalde, Jessica, Astudillo, Daniela Estefania, Agraz, Irene, Lopez-Mendoza, Manuel, de Arriba, Gabriel, Corchete, Elena, Quiroga, Borja, Gutierrez, Maria Jose, Martin-Conde, Maria Luisa, Lopes, Vanessa, Ramos, Carmela, Mendez, Irene, Cao, Mercedes, Dominguez, Fernando, and Ortiz, Alberto
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- 2021
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26. An update on the use of tolvaptan for autosomal dominant polycystic kidney disease: consensus statement on behalf of the ERA Working Group on Inherited Kidney Disorders, the European Rare Kidney Disease Reference Network and Polycystic Kidney Disease International
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Roman-Ulrich Müller, A. Lianne Messchendorp, Henrik Birn, Giovambattista Capasso, Emilie Cornec-Le Gall, Olivier Devuyst, Albertien van Eerde, Patrick Guirchoun, Tess Harris, Ewout J. Hoorn, Nine V.A.M. Knoers, Uwe Korst, Djalila Mekahli, Yannick Le Meur, Tom Nijenhuis, Albert C.M. Ong, John A. Sayer, Franz Schaefer, Aude Servais, Vladimir Tesar, Roser Torra, and Stephen B. Walsh and Ron T. Gansevoort
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Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
No abstract
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- 2022
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27. Are Kidney Cysts More Frequent in Individuals With COL4A3-COL4A4 Pathogenic Variants?: PUB197
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Teran, Melissa Pilco, Furlano, Monica, Jimenez, Víctor Martinez, Pybus, Marc, vanessa Pérez gómez, María, Peris, Asunción Rius, de Arizón, Leonor Fayos, Berná, Gerson, Mancera, Jonathan Hernandez, Pérez, Hugo Vergara, Ars, Elisabet, and Torra, Roser
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- 2022
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28. Reply to Comments on the SENefro Consensus Document on Autosomal Dominant Polycystic Kidney Disease
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Alberto Ortiz, Elisabet Ars, Carmen Bernis, Gloria Fraga, Mónica Furlano, Víctor Martínez, Judith Martins, Maria Vanessa Pérez-Gómez, José Carlos Rodríguez-Pérez, Laia Sans, and Roser Torra
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2023
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29. Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease
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José Luis Gorriz, David Arroyo, Luis D’Marco, Roser Torra, Patricia Tomás, María Jesús Puchades, Nayara Panizo, Jonay Pantoja, Marco Montomoli, José Luis Llisterri, Vicente Pallares-Carratalá, and José Manuel Valdivielso
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Autosomal dominant polycystic kidney disease ,Chronic kidney disease ,Cardiovascular disease ,Nephropathy ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. Methods We evaluated 2445 CKD patients (2010–2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. Results ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels
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- 2021
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30. A Mild Presentation of X-Linked Hypophosphatemia Caused by a Non-Canonical Splice Site Variant in the PHEX Gene.
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Fraga, Gloria, Herreros, M. Alba, Pybus, Marc, Aza-Carmona, Miriam, Pilco-Teran, Melissa, Furlano, Mónica, García-Borau, M. José, Torra, Roser, and Ars, Elisabet
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GENETIC variation ,HYPOPHOSPHATEMIA ,GENETIC testing ,GENETIC engineering ,SYMPTOMS ,POLYCYSTIC kidney disease - Abstract
X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the PHEX gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the PHEX gene. Segregation analysis detected that the consultand's father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand's son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the PHEX gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the PHEX gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of PHEX transcripts with aberrant and wild-type splicing. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1
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Olinger, Eric, Hofmann, Patrick, Kidd, Kendrah, Dufour, Inès, Belge, Hendrica, Schaeffer, Céline, Kipp, Anne, Bonny, Olivier, Deltas, Constantinos, Demoulin, Nathalie, Fehr, Thomas, Fuster, Daniel G., Gale, Daniel P., Goffin, Eric, Hodaňová, Kateřina, Huynh-Do, Uyen, Kistler, Andreas, Morelle, Johann, Papagregoriou, Gregory, Pirson, Yves, Sandford, Richard, Sayer, John A., Torra, Roser, Venzin, Christina, Venzin, Reto, Vogt, Bruno, Živná, Martina, Greka, Anna, Dahan, Karin, Rampoldi, Luca, Kmoch, Stanislav, Bleyer, Anthony J., Sr., and Devuyst, Olivier
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- 2020
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32. Recommendations for the management of renal involvement in tuberous sclerosis complex
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Ariceta, Gema, Buj, María José, Furlano, Mónica, Martínez, Víctor, Matamala, Anna, Morales, Montserrat, Robles, Nicolás Roberto, Sans, Laia, Villacampa, Felipe, and Torra, Roser
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- 2020
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33. Recommendations for the management of renal involvement in tuberous sclerosis complex
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Gema Ariceta, María José Buj, Mónica Furlano, Víctor Martínez, Anna Matamala, Montserrat Morales, Nicolás Roberto Robles, Laia Sans, Felipe Villacampa, and Roser Torra
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Angiomiolipomas ,Esclerosis tuberosa ,Enfermedad renal poliquística ,Síndrome del gen contiguo ,Quistes ,Proteína mTOR ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Tuberous sclerosis complex (TSC) is a rare, hereditary, multisystemic disease with a broad phenotypic spectrum. Its management requires the collaboration of multiple specialists. Just as in the paediatric age, the paediatric neurologist takes on special importance; in adulthood, renal involvement is the cause of the greatest morbidity and mortality. There are several recommendations on the general management of patients with TSC but none that focuses on renal involvement. These recommendations respond to the need to provide guidelines to facilitate a better knowledge and diagnostic-therapeutic management of the renal involvement of TSC through a rational use of complementary tests and the correct use of available treatments. Their elaboration has been based on consensus within the hereditary renal diseases working group of the S.E.N./REDINREN (Spanish Society of Nephrology/Kidney Research Network). It has also counted on the participation of non-nephrologist specialists in TSC in order to expand the vision of the disease. Resumen: El complejo esclerosis tuberosa (CET) es una enfermedad rara, hereditaria, multisistémica y con un amplio espectro fenotípico. Su manejo requiere de la colaboración de múltiples especialistas. Así como en la edad pediátrica cobra un especial relieve el neurólogo pediatra, en la edad adulta la afectación renal es la causante de la mayor morbimortalidad. Existen diversas recomendaciones sobre el manejo general del paciente con CET pero ninguna que se centre en la afectación renal. Las presentes recomendaciones responden a la necesidad de proporcionar pautas para facilitar un mejor conocimiento y manejo diagnóstico-terapéutico de la afectación renal del CET mediante un uso racional de las pruebas complementarias y el empleo correcto de los tratamientos disponibles. Su elaboración se ha basado en el consenso dentro del grupo de trabajo de enfermedades renales hereditarias de la S.E.N./REDINREN. Ha contado con la participación de especialistas en CET no nefrólogos también con el fin de ampliar la visión de la enfermedad.
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- 2020
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34. The Benefits of Early versus Late Therapeutic Intervention in Fabry Disease
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Mónica Furlano, Elisabet Ars, Anna Matamala, Vicens Brossa, Joan Martí, Maria del Prado-Venegas, Jaume Crespi, Esther Roe, and Roser Torra
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Genetics ,QH426-470 - Abstract
Background. Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention). Conclusions. These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.
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- 2022
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35. Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease
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Gorriz, José Luis, Arroyo, David, D’Marco, Luis, Torra, Roser, Tomás, Patricia, Puchades, María Jesús, Panizo, Nayara, Pantoja, Jonay, Montomoli, Marco, Llisterri, José Luis, Pallares-Carratalá, Vicente, and Valdivielso, José Manuel
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- 2021
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36. Corrigendum to 'Long-term follow-up of renal function in patients treated with migalastat for Fabry disease' [Bichet et al., MGM Reports; 28 (2021) 100786]
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Daniel G. Bichet, Roser Torra, Eric Wallace, Derralynn Hughes, Roberto Giugliani, Nina Skuban, Eva Krusinska, Ulla Feldt-Rasmussen, Raphael Schiffmann, and Kathy Nicholls
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Published
- 2021
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37. Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression
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Borja Quiroga and Roser Torra
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autosomal dominant polycystic kidney disease ,tolvaptan ,aquaresis ,diet ,nutrition ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan.
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- 2022
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38. International consensus statement on the diagnosis and management of autosomal dominant polycystic kidney disease in children and young people
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Gimpel, Charlotte, Bergmann, Carsten, Bockenhauer, Detlef, Breysem, Luc, Cadnapaphornchai, Melissa A., Cetiner, Metin, Dudley, Jan, Emma, Francesco, Konrad, Martin, Harris, Tess, Harris, Peter C., König, Jens, Liebau, Max C., Marlais, Matko, Mekahli, Djalila, Metcalfe, Alison M., Oh, Jun, Perrone, Ronald D., Sinha, Manish D., Titieni, Andrea, Torra, Roser, Weber, Stefanie, Winyard, Paul J. D., and Schaefer, Franz
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- 2019
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39. Long-term follow-up of renal function in patients treated with migalastat for Fabry disease
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Daniel G. Bichet, Roser Torra, Eric Wallace, Derralynn Hughes, Roberto Giugliani, Nina Skuban, Eva Krusinska, Ulla Feldt-Rasmussen, Raphael Schiffmann, and Kathy Nicholls
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Classic phenotype ,Efficacy ,Fabry disease ,Chaperone ,Migalastat ,Renal function ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)–naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91.4 mL/min/mL/1.73 m2) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m2) patients with amenable variants who received migalastat 123 mg every other day for ≥2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFRCKD-EPI were − 1.6 mL/min/1.73 m2 overall and − 1.8 mL/min/1.73 m2 and − 1.4 mL/min/1.73 m2 in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFRCKD-EPI were − 1.6 mL/min/1.73 m2 overall and − 2.6 mL/min/1.73 m2 and − 0.8 mL/min/1.73 m2 in male and female patients, respectively. Mean annualized rate of change in eGFRCKD-EPI in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [α-Gal A] activity of
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- 2021
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40. MYH9 Associated nephropathy
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Furlano, Mónica, Arlandis, Rosa, del Prado Venegas, María, Novelli, Silvana, Crespi, Jaume, Bullich, Gemma, Ayasreh, Nadia, Remacha, Ángel, Ruiz, Patricia, Lorente, Laura, Ballarín, José, Matamala, Anna, Ars, Elisabet, and Torra, Roser
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- 2019
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41. A step-wise approach for establishing a multidisciplinary team for the management of tuberous sclerosis complex: a Delphi consensus report
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Stéphane Auvin, John J. Bissler, Vincent Cottin, Ayataka Fujimoto, Günther F. L. Hofbauer, Anna C. Jansen, Sergiusz Jóźwiak, Larissa Kerecuk, J. Christopher Kingswood, Romina Moavero, Roser Torra, and Vicente Villanueva
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Tuberous sclerosis complex ,Multidisciplinary care ,Multidisciplinary team ,Medicine - Abstract
Abstract Background Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder associated with mutations in TSC1 and TSC2 genes, upregulation of mammalian target of rapamycin signaling, and subsequent tumor formation in various organs. Due to the many manifestations of TSC and their potential complications, management requires the expertise of multiple medical disciplines. A multidisciplinary care approach is recommended by consensus guidelines. Use of multidisciplinary teams (MDTs) has been shown to be beneficial in treating other complex diseases, such as cancer. In a lifelong disease such as TSC, an MDT may facilitate the transition from pediatric to adult care. However, little guidance exists in the literature regarding how to organize an MDT in TSC. Methods To discuss the best approach to assembling an MDT, this project was initiated in October 2017 with a meeting of 12 physicians from various specialties and various countries. Following this first meeting, the experts generated statements on the most important aspects to implement in establishing an MDT for TSC by 3 rounds of selection using a Delphi process via electronic correspondence. Finally, TSC patient advocates reviewed the findings and provided additional insights from a patient perspective. Results A 3-step roadmap was recommended, starting with identifying a single individual to begin organizing care (Step 1), then establishing a small core team (Step 2), and finally, establishing a larger multi-disciplinary team (Step 3). Because of the multisystemic nature of TSC, the MDT should include specialists such as a neurologist, a neurosurgeon, a nephrologist, a urologist, a pulmonologist, an ophthalmologist, a cardiologist, a dermatologist, a geneticist, and a psychiatrist/psychologist. The MDT should recommend a care plan for each patient based on the individual’s needs and in consultation with him/her or his/her family. Some of the most important aspects of an MDT that were agreed upon included identifying a case manager to help coordinate care, providing access to health care professionals of varying specialties, and including a lead physician who takes medical responsibility for patients’ overall care. Conclusions The results of our consensus provide guidance to support the initiation of an MDT in TSC.
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- 2019
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42. Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome: case report and review of the literature
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Andrea Domingo-Gallego, Mónica Furlano, Marc Pybus, Daniel Barraca, Ana Belén Martínez, Emiliano Mora Muñoz, Roser Torra, and Elisabet Ars
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Galloway-Mowat syndrome ,Nephrotic syndrome ,OSGEP ,KEOPS complex ,Genetic testing ,Case report ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies. WDR73 pathogenic variants were described as the first genetic cause of GAMOS and, very recently, four novel causative genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. Case presentation We present the clinical and genetic characteristics of two unrelated infants with clinical suspicion of GAMOS who were born from consanguineous parents. Both patients showed a similar clinical presentation, with early-onset nephrotic syndrome, microcephaly, brain atrophy, developmental delay, axial hypotonia, and early fatality. We identified two novel likely disease-causing variants in the OSGEP gene. These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants. Conclusions Our findings expand the spectrum of pathogenic variants in the OSGEP gene and, taken in conjunction with the results of the literature review, suggest that the OSGEP gene should be considered the main known monogenic cause of GAMOS. Early genetic diagnosis of GAMOS is of paramount importance for genetic counseling and family planning.
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- 2019
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43. MYH9 Associated nephropathy
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Mónica Furlano, Rosa Arlandis, María del Prado Venegas, Silvana Novelli, Jaume Crespi, Gemma Bullich, Nadia Ayasreh, Ángel Remacha, Patricia Ruiz, Laura Lorente, José Ballarín, Anna Matamala, Elisabet Ars, and Roser Torra
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Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. The disorder is characterized by the presence of macrothrombocytopenia, leukocyte inclusions and a variable risk of developing renal failure, hearing loss and early-onset cataracts. We describe the case of a 27-year-old Caucasian woman, diagnosed initially with idiopathic thrombocytopenic purpura. After a detailed family history and the appearance of renal involvement and hearing loss, genetic testing allowed to make the diagnosis of nephropathy associated with MYH9 mutation. This case is an example of the delayed diagnosis of uncommon diseases and highlights the usefulness genetic testing. A review of the disease is provided. Resumen: Las enfermedades relacionadas con mutaciones del gen MYH9 son un grupo de patologías genéticas raras. Su herencia sigue un patrón autosómico dominante en donde el gen MYH9, codifica la cadena pesada de la miosina IIA no muscular que se expresa en diferentes tejidos pero especialmente en los podocitos y en las células mesangiales. Este trastorno se caracteriza por la presencia de macrotrombocitopenia, inclusiones leucocitarias y un riesgo variable de desarrollar insuficiencia renal, hipoacusia y cataratas en edad juvenil o adulta. Describimos el caso de una mujer de 27 años, de raza caucásica, diagnosticada inicialmente de púrpura trombocitopénica idiopática. Tras una detallada historia familiar y el desarrollo de síntomas clínicos posteriores con afectación renal e hipoacusia, se le realizó un estudio genético que nos permitió el diagnóstico de nefropatía asociada a la mutación en el gen MYH9. Este caso destaca el retraso del diagnóstico y la utilidad del estudio genético en pacientes con enfermedades muy poco frecuentes. Se procede a la revisión de la enfermedad en este artículo. Keywords: MYH9 nephropathy, Hearing loss, Thrombocytopenia, Alport syndrome, Epstein syndrome, May-Hegglin anomaly, Palabras clave: Nefropatía MYH9, Hipoacusia, Trombocitopenia, Síndrome de Alport, Síndrome de Epstein, Anomalía de May-Hegglin, Sindrome de Sebastián
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- 2019
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44. Expert consensus guidelines for the genetic diagnosis of Alport syndrome
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Savige, Judy, Ariani, Francesca, Mari, Francesca, Bruttini, Mirella, Renieri, Alessandra, Gross, Oliver, Deltas, Constantinos, Flinter, Frances, Ding, Jie, Gale, Daniel P., Nagel, Mato, Yau, Michael, Shagam, Lev, Torra, Roser, Ars, Elisabet, Hoefele, Julia, Garosi, Guido, and Storey, Helen
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- 2019
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45. FollowME Fabry Pathfinders Registry: Renal effectiveness in a cohort of patients on migalastat treatment for at least three years
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West, Michael L., Hughes, Derralynn, Sunder-Plassmann, Gere, Jovanovic, Ana, Brand, Eva, Bichet, Daniel G., Pisani, Antonio, Nowak, Albina, Torra, Roser, Khan, Aneal, Azevedo, Olga, Lehman, Anna, Linhart, Aleš, Rutecki, Jasmine, Giuliano, Joseph D., Krusinska, Eva, and Nordbeck, Peter
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- 2024
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46. Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative
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Derralynn A Hughes, Raphael Schiffmann, Ales Linhart, Patricio Aguiar, Patrick B Deegan, Fatih Ezgu, Andrea Frustaci, Olivier Lidove, Jean-Claude Lubanda, Kathleen Nicholls, Dau-Ming Niu, Uma Ramaswami, Ricardo Reisin, Paula Rozenfeld, Einar Svarstad, Roser Torra, Bojan Vujkovac, Michael L West, Jack Johnson, and Mark J Rolfe
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Medicine - Abstract
Objectives The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation.Design and setting Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists’ free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed.Results A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages.Conclusions PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.
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- 2020
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47. Fabry Nephropathy: An Evidence-Based Narrative Review
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María del Pino, Amado Andrés, Ana Ávila Bernabéu, Joaquín de Juan-Rivera, Elvira Fernández, Juan de Dios García Díaz, Domingo Hernández, José Luño, Isabel Martínez Fernández, José Paniagua, Manuel Posada de la Paz, José Carlos Rodríguez-Pérez, Rafael Santamaría, Roser Torra, Joan Torras Ambros, Pedro Vidau, and Josep-Vicent Torregrosa
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Fabry disease ,Nephropathy ,Proteinuria ,Enzyme replacement therapy ,Inherited disorder ,Dermatology ,RL1-803 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.
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- 2018
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48. Integration-free induced pluripotent stem cells derived from a patient with autosomal recessive Alport syndrome (ARAS)
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Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, and Angel Raya
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Biology (General) ,QH301-705.5 - Abstract
A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. This iPSC line offers a useful resource to study Alport syndrome pathomechanisms and drug testing.
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- 2017
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49. Generation of integration-free induced pluripotent stem cell lines derived from two patients with X-linked Alport syndrome (XLAS)
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Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, and Angel Raya
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. These iPSC lines offer a useful resource to study Alport syndrome pathomechanisms and drug testing.
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- 2017
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50. A review on autosomal dominant tubulointerstitial kidney disease
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Ayasreh, Nadia, Miquel, Rosa, Matamala, Ana, Ars, Elisabet, and Torra, Roser
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- 2017
- Full Text
- View/download PDF
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