title: Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort.
abstract: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies.
  
  
  
  Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point.
  
  
  
  Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD.
  
  
  
  CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.
authors.affiliation: Children's Hospital, Poznan, Poland.|Polish Registry of Inherited Tubulopathies (POLtube), Polish Society of Pediatric Nephrology, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Zaniew
authors.affiliation: Department of Pediatrics, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Bökenkamp
authors.affiliation: Children's Hospital, Poznan, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kolbuc
authors.affiliation: Nephrology and Dialysis Unit, Department of Woman, Child and Urological Diseases, Azienda Ospedaliero-Universitaria 'Sant'Orsola-Malpighi', Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: La Scola
authors.affiliation: Endocrinology Unit, Department of Woman, Child and Urological Diseases, Azienda Ospedaliero-Universitaria 'Sant'Orsola-Malpighi', Bologna, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Baronio
authors.affiliation: Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Niemirska
authors.affiliation: Chair and Clinical Department of Pediatrics, SMDZ in Zabrze, SUM in Katowice, Katowice, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Szczepanska
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Münster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bürger
authors.affiliation: Department of Pediatrics, II University of Naples, Naples, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: La Manna
authors.affiliation: Department of Pediatric Nephrology, Collegium Medicum of the Jagiellonian University, Cracow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Miklaszewska
authors.affiliation: Department of Pediatrics, Immunology and Nephrology, Polish Mothers Memorial Hospital Research Institute, Lódz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Rogowska-Kalisz
authors.affiliation: Department of Pediatric Nephrology, Charité Universitätsmedizin Berlin, Charité Children's Hospital, Berlin, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gellermann
authors.affiliation: Pediatric Nephrology, 'A. and P. Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Argyroula
authors.initials: A
authors.lastname: Zampetoglou
authors.affiliation: Department of Pediatrics and Nephrology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wasilewska
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Roszak
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Moczko
authors.affiliation: Department of Nephrology, Children's Hospital, Katowice, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Krzemien
authors.affiliation: Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Runowski
authors.affiliation: Dialysis Center, District Hospital, Rzeszów, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Siten
authors.affiliation: Department of Pediatrics, Medical University of Gdansk, Nephrology and Hypertension, Gdansk, Poland.
authors.forename: Iga
authors.initials: I
authors.lastname: Zaluska-Lesniewska
authors.affiliation: Pediatric Nephrology, Hospital G.Brotzu, Cagliari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fonduli
authors.affiliation: Pediatric Nephrology, Hospital G.Brotzu, Cagliari, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Zurrida
authors.affiliation: Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Paglialonga
authors.affiliation: University Children's Hospital, Medical Faculty Skopje, Skopje, Macedonia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gucev
authors.affiliation: Nephrology Department, University Children's Hospital, Belgrade, Serbia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Paripovic
authors.affiliation: Division of Nephrology, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: Rina
authors.initials: R
authors.lastname: Rus
authors.affiliation: Mater Dei Hospital, Msida, Malta.
authors.forename: Valerie
authors.initials: V
authors.lastname: Said-Conti
authors.affiliation: Department of Pediatric and Adolescent Medicine, Skåne University Hospital, Lund, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sartz
authors.affiliation: Department of Pediatrics, Inje University Busan Paik Hospital, Busan, Korea.
authors.forename: Woo Yeong
authors.initials: WY
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Ajou University Daewoo Hospital, Geoje, Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Ehwa University Mokdong Hospital, Seoul, Korea.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Yong Hoon
authors.initials: YH
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Polish Registry of Inherited Tubulopathies (POLtube), Polish Society of Pediatric Nephrology, Poland.|Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sikora
authors.affiliation: Pediatric Nephrology, 'A. and P. Kyriakou' Children's Hospital, Athens, Greece.
authors.forename: Constantinos J
authors.initials: CJ
authors.lastname: Stefanidis
authors.affiliation: University Children's Hospital, Medical Faculty Skopje, Skopje, Macedonia.
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.affiliation: Department of General Pediatrics, University Children's Hospital, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.affiliation: Laboratory of Histomorphology and Molecular Biology of the Kidney, Department of Medicine, University of Padova, Padova, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Anglani
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Addis
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: University College London, Institute of Child Health and Great Ormond Street Hospital for Children, National Health Service Trust, London, UK.
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D053565:Hypercalciuria / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000453:epidemiology* / Q000235:genetics; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011507:Proteinuria / Q000453:epidemiology* / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human
keywords: Dent-2 disease; Lowe syndrome; OCRL; chronic kidney disease; nephrocalcinosis