title: Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome.
abstract: Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis.
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Goettingen, Goettingen, Germany.
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authors.initials: O
authors.lastname: Gross
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Clifford E
authors.initials: CE
authors.lastname: Kashtan
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Rheault
authors.affiliation: Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Frances
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authors.affiliation: Melbourne Health, The University of Melbourne, Parkville, VIC, Australia.
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authors.affiliation: Division of Nephrology, Washington University School of Medicine, St Louis, MO, USA.
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authors.initials: JH
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authors.affiliation: Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma de Barcelona and REDINREN, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
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authors.affiliation: Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma de Barcelona and REDINREN, Barcelona, Spain.
authors.forename: Elisabet
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authors.affiliation: Molecular Medicine Research Center, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
authors.forename: Constantinos
authors.initials: C
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authors.affiliation: Molecular Medicine Research Center, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
authors.forename: Isavella
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authors.affiliation: University of Southern California, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Laura
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authors.affiliation: Medical Genetics Unit, University of Siena, Siena, Italy.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.affiliation: Medical Genetics Unit, University of Siena, Siena, Italy.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ariani
authors.affiliation: Medical Genetics Unit, University of Siena, Siena, Italy.|Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
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authors.initials: F
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authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
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authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Parminder
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authors.affiliation: Division de Néphrologie, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France.|Université Paris Descartes, Paris, France.
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authors.lastname: Knebelman
authors.affiliation: Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA) Service de Néphrologie Pédiatrique, Clinique Maurice Lamy, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Heidet
authors.affiliation: Alport Syndrome Foundation, Phoenix, AZ, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lagas
authors.affiliation: Alport Foundation of Australia, Valentine, NSW, Australia.
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authors.affiliation: University College London-Centre for Nephrology, London, UK.
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authors.affiliation: New Indications Discovery Unit, Translational Medicine, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
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authors.initials: LCG
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authors.forename: Sebastien
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authors.lastname: Vallee
authors.affiliation: Association for Information and Research on Genetic Renal Diseases (AIRG)-France, Paris, France.|Federation of European Associations of patients affected by Genetic Renal Diseases, FEDERG, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Renault
authors.affiliation: Alport Israel, Israel.
authors.forename: Julia
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authors.lastname: Schifter
authors.affiliation: Alport UK, Tetbury, UK.
authors.forename: Jules
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authors.lastname: Skelding
authors.affiliation: Alport UK, Tetbury, UK.
authors.forename: Susie
authors.initials: S
authors.lastname: Gear
authors.affiliation: Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.affiliation: Renal Medicine, Royal Infirmary, University of Edinburgh, Edinburgh, UK.
authors.forename: A Neil
authors.initials: AN
authors.lastname: Turner
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Rachel
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authors.lastname: Lennon
mesh_terms: D000818:Animals; D024141:Collagen Type IV / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D020380:Needs Assessment; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000628:therapy; D050199:Podocytes; D058996:Quality Improvement
chemical_list: D024141:Collagen Type IV
keywords: Alport syndrome; chronic kidney disease; guidelines; hereditary kidney disease; nephroprotection