title: Observations of a large Dent disease cohort.
abstract: Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France; INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France; Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Centre of Clinical Research, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France. Electronic address: anne.blanchard@egp.aphp.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.affiliation: Paris Descartes University, Faculty of Pharmacy, Laboratory of Biomathematics, Sorbonne Paris Cité, F-75005 Paris, France; INSERM, UMR 1144, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Curis
authors.affiliation: University Hospital of Lille, Jeanne of Flanders Hospital, Nephrology, Lille, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Guyon-Roger
authors.affiliation: Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Genetics Department, Paris, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Kahila
authors.affiliation: Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Genetics Department, Paris, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Treard
authors.affiliation: Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Department of Pediatric Nephrology, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Baudouin
authors.affiliation: University Hospital of Nice, Department of Pediatric Nephrology, Nice, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Bérard
authors.affiliation: University Hospital of Angers, Department of Pediatrics, LUNAM, Angers, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Champion
authors.affiliation: Reference Centre of Rare Renal Diseases, Department of Pediatric Nephrology Rheumatology and Dermatology, Hospices Civils de Lyon, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.affiliation: Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Centre of Clinical Research, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dubourg
authors.affiliation: University Hospital of Bordeaux, Department of Nephrology Dialysis Transplantation, Bordeaux, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: de la Faille
authors.affiliation: Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium; Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Department of Pediatric Nephrology, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Deschenes
authors.affiliation: University Hospital Hautepierre, Department of Pediatrics, Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.affiliation: University Hospital of Bordeaux, Department of Pediatric Nephrology, Bordeaux, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Harambat
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Department of Physiology, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Houillier
authors.affiliation: Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Department of Nephrology, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Karras
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Necker-Enfants Malades University Hospital, Department of Pediatric Nephrology, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.affiliation: University Hospital of Saint Etienne, North Hospital, Department of Pediatrics, Saint Etienne, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Lavocat
authors.affiliation: Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Department of Pediatric Nephrology, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.affiliation: University Hospital of Tours, Pediatric Nephrology Department, Tours, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Merieau
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; University Hospital of Saint Etienne, North Hospital, Department of Pediatrics, Saint Etienne, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.affiliation: University Hospital of Besancon, Unit of Pediatric Nephrology, Besançon, France.
authors.forename: François
authors.initials: F
authors.lastname: Nobili
authors.affiliation: University Hospital Jeanne de Flandre, Pediatric Nephrology Department, Lille, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Novo
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; University Hospital of Saint Etienne, North Hospital, Department of Pediatrics, Saint Etienne, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.affiliation: Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, Trousseau University Hospital, Department of Nephrology and Kidney Transplantation, Paris, France.
authors.forename: Tim
authors.initials: T
authors.lastname: Ulinski
authors.affiliation: University Paris Descartes, Faculty of Medicine, Paris, France; INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Genetics Department, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaître
authors.affiliation: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Genetics Department, Paris, France.
authors.forename: Rosa
authors.initials: R
authors.lastname: Vargas-Poussou
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000652:urine; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics / Q000652:urine; D017674:Hypophosphatemia / Q000097:blood / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053040:Nephrolithiasis / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000652:urine; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011507:Proteinuria / Q000235:genetics / Q000652:urine; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human
keywords: Dent disease; hypercalciuria-hypokalemia; proteinuria; renal failure