title: Alport syndrome from bench to bedside: the potential of current treatment beyond RAAS blockade and the horizon of future therapies.
abstract: The hereditary type IV collagen disease Alport syndrome (AS) always leads to end-stage renal failure. Yesterday, for the past 90 years, this course was described as 'inevitable'. Today, RAAS blockade has changed the 'inevitable' course to a treatable disease. Tomorrow, researchers hope to erase the 'always' from 'always leads to renal failure' in the textbooks. This review elucidates therapeutic targets that evolve from research: (i) kidney embryogenesis and pathogenesis; (ii) phenotype-genotype correlation and the role of collagen receptors and podocytes; (iii) the malfunctioning Alport-GBM; (iv) tubulointerstitial fibrosis; (v) the role of proteinuria in pathogenesis and prognosis; and (vi) secondary events such as infections, hyperparathyroidism and hypercholesterolaemia. Therefore, moderate lifestyle, therapy of bacterial infections, Paricalcitol in adult patients with hyperparathyroidism and HMG-CoA-reductase inhibitors in adult patients with dyslipoproteinemia might contribute to a slower progression of AS and less cardiovascular events. In the future, upcoming treatments including stem cells, chaperon therapy, collagen receptor blockade and anti-microRNA therapy will expand our perspective in protecting the kidneys of Alport patients from further damage. This perspective on current and future therapies is naturally limited by our personal focus in research, but aims to motivate young scientists and clinicians to find a multimodal cure for AS.
authors.affiliation: Clinic of Nephrology and Rheumatology, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gross
authors.affiliation: Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Perin
authors.affiliation: Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Deltas
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D024141:Collagen Type IV / Q000235:genetics; D006801:Humans; D009394:Nephritis, Hereditary / Q000235:genetics / Q000628:therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects*
chemical_list: D057911:Angiotensin Receptor Antagonists; D024141:Collagen Type IV
keywords: Alport syndrome; chaperon therapy; discoidin domain receptor 1; kidney fibrosis; microRNA-21