Sergio C Lopez-Garcia1,2, Mallory L Downie1,2, Ji Soo Kim2, Olivia Boyer3, Stephen B Walsh1, Tom Nijenhuis4, Svetlana Papizh5, Pallavi Yadav5, Ben C Reynolds5, Stéphane Decramer6, Martine Besouw7, Manel Perelló Carrascosa8, Claudio La Scola9, Francesco Trepiccione10, Gema Ariceta11, Aurélie Hummel12, Claire Dossier13, John A Sayer14,15,16, Martin Konrad17, Mandy G Keijzer-Veen18, Atif Awan19, Biswanath Basu20, Dominique Chauveau21, Leire Madariaga22, Linda Koster-Kamphuis23, Mónica Furlano24, Miriam Zacchia10, Pierluigi Marzuillo25, Yincent Tse26, Ismail Dursun27, Ayse Seda Pinarbasi27, Despoina Tramma28, Ewout J Hoorn29, Ibrahim Gokce30, Kathleen Nicholls31,32, Loai A Eid33, Lisa Sartz34, Michael Riordan19, Nakysa Hooman35, Nikoleta Printza36, Olivier Bonny37, Pedro Arango Sancho38, Raphael Schild39, Rajiv Sinha40, Stefano Guarino25, Victor Martinez Jimenez41, Lidia Rodríguez Peña42, Hendrica Belge43, Olivier Devuyst44, Tanja Wlodkowski45, Francesco Emma46, Elena Levtchenko47, Nine V A M Knoers48,49, Daniel G Bichet50, Franz Schaefer45, Robert Kleta1,2, Detlef Bockenhauer1,2. 1. Department of Renal Medicine, University College London, London,UK. 2. Paediatric Nephrology Unit, Great Ormond Street Hospital, London,UK. 3. Department of Pediatric Nephrology, Reference Center for Hereditary Kidney Diseases (MARHEA), Laboratory of Hereditary Kidney Diseases, Imagine Institute, INSERM U1163, Paris Descartes University, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris,France. 4. Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboudumc Expertisecentrum Zeldzame Nierziekten, Radboud University Medical Center, Nijmegen, TheNetherlands. 5. Department of Hereditary and Acquired Kidney Diseases, Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russian Federation. 6. Department of Paediatric Nephrology, Leeds Teaching Hospitals NHS Trust, Leeds,UK. 7. Department of Paediatric Nephrology, Royal Hospital for Children, Glasgow,UK. 8. Department of Nephrology, Vall d'Hebron University Hospital, Barcelona,Spain. 9. Nephrology and Dialysis Unit, Department of Woman, Child and Urological Diseases, Azienda Ospedaliero-Universitaria Sant'Orsola-Malpighi, Bologna,Italy. 10. Department of Translational Medical Sciences, University of Campania "L.Vanvitelli", Naples,Italy. 11. Department of Paediatric Nephrology, Hospital Universitario Vall d'Hebron, Barcelona,Spain. 12. Department of Nephrology and Transplantation, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris,France. 13. Department of Paediatric Nephrology, Hôpital Robert-Debre, Paris,France. 14. Translational and Clinical Medicine Institute, Faculty of Medical Sciences, Newcastle University, Central Parkway, Newcastle Upon Tyne,UK. 15. Renal Services, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne,UK. 16. NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne,UK. 17. Department of Paediatric Nephrology, University Children's Hospital, Münster,Germany. 18. Department of Pediatric Nephrology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, TheNetherlands. 19. Department of Paediatric Nephrology, Temple Street Children's University Hospital, Dublin,Ireland. 20. Division of Pediatric Nephrology, Department of Pediatrics, N. R. S. Medical College & Hospital, Kolkata,India. 21. Department of Nephrology and Transplantation, Centre de Référence des Maladies Rénales Rares, Centre Hospitalier Universitaire de Toulouse, Université Toulouse-III, Toulouse,France. 22. Department of Paediatric Nephrology, Cruces University Hospital, IIS Biocruces-Bizkaia, University of the Basque Country, Bizkaia,Spain. 23. Department of Paediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, TheNetherlands. 24. Inherited Kidney Diseases, Nephrology Department, Fundació Puigvert, Instituto de Investigaciones Biomédicas Sant Pau (IIB-Sant Pau), Department of Medicine-Universitat Autónoma de Barcelona, REDinREN, Instituto de Investigación Carlos III, Barcelona,Spain. 25. Department of Women, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples,Italy. 26. Department of Paediatric Nephrology, Great North Children's Hospital, Newcastle Upon Tyne,UK. 27. Department of Paediatrics, Division of Nephrology, Erciyes University Faculty of Medicine, Kayseri,Turkey. 28. 4th Department of Pediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki,Greece. 29. Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, TheNetherlands. 30. Department of Paediatric Nephrology, Marmara University, Faculty of Medicine, İstanbul,Turkey. 31. Department of Nephrology, Royal Melbourne Hospital, Parkville,Australia. 32. Department of Nephrology, University of Melbourne, Parkville,Australia. 33. Department of Paediatric Nephrology, Dubai Hospital-Dubai Health Authority, Dubai, United Arab Emirates. 34. Department of Clinical Sciences, Paediatric nephrology, Skåne University hospital, Lund University, Lund,Sweden. 35. Aliasghar Clinical Research Development Center (ACRDC), Aliasghar Children Hospital, Iran University of Medical Sciences, Tehran,Iran. 36. 1st Paediatric Department, Aristotle University, Thessaloniki,Greece. 37. Service of Nephrology, Rue du Bugnon 17, Lausanne University Hospital, Lausanne,Switzerland. 38. Department of Paediatric Nephrology and Transplantation, Hospital Sant Joan De Déu, Esplugues De Llobregat, Barcelona,Spain. 39. Department of Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg,Germany. 40. Division of Paediatric Nephrology, Institute of Child Health, Kolkata,India. 41. Department of Nephrology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia,Spain. 42. Section of Medical Genetics, Department of Pediatrics, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia,Spain. 43. Center of Human Genetics, Institut de Pathologie et Genetique, Gosselies,Belgium. 44. Institute of Physiology, Zurich Center for Integrative Human Physiology (ZHIP), Mechanism of Inherited Kidney Disorders Group, University of Zurich, Zurich,Switzerland. 45. Department of Paediatric Nephrology, University Children's Hospital, Heidelberg,Germany. 46. Division of Nephrology, Department of Pediatric Subspecialties, Bambino Gesù Children's Hospital, IRCCS, Rome,Italy. 47. Department of development and regeneration, Laboratory of Paediatric Nephrology, University Hospital, Leuven,Belgium. 48. Department of Genetics, Center for Molecular Medicine, University Medical Centre Utrecht, Utrecht University, Utrecht, TheNetherlands. 49. Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, TheNetherlands. 50. Nephrology Service, Department of Medicine, Pharmacology and Physiology, University of Montreal, Montreal, Quebec,Canada.
Abstract
BACKGROUND: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. METHODS: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. RESULTS: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. CONCLUSION: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.
BACKGROUND:Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. METHODS: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. RESULTS: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. CONCLUSION: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.