Marcin Zaniew1,2, Arend Bökenkamp3, Marcin Kolbuc1, Claudio La Scola4, Federico Baronio5, Anna Niemirska6, Maria Szczepanska7, Julia Bürger8, Angela La Manna9, Monika Miklaszewska10, Anna Rogowska-Kalisz11, Jutta Gellermann12, Argyroula Zampetoglou13, Anna Wasilewska14, Magdalena Roszak15, Jerzy Moczko15, Aleksandra Krzemien16, Dariusz Runowski6, Grzegorz Siten17, Iga Zaluska-Lesniewska18, Patrizia Fonduli19, Franca Zurrida19, Fabio Paglialonga20, Zoran Gucev21, Dusan Paripovic22, Rina Rus23, Valerie Said-Conti24, Lisa Sartz25, Woo Yeong Chung26, Se Jin Park27, Jung Won Lee28, Yong Hoon Park29, Yo Han Ahn30, Przemyslaw Sikora2,31, Constantinos J Stefanidis13, Velibor Tasic21, Martin Konrad8, Franca Anglani32, Maria Addis33, Hae Il Cheong34, Michael Ludwig35, Detlef Bockenhauer36. 1. Children's Hospital, Poznan, Poland. 2. Polish Registry of Inherited Tubulopathies (POLtube), Polish Society of Pediatric Nephrology, Poland. 3. Department of Pediatrics, VU Medical Center, Amsterdam, The Netherlands. 4. Nephrology and Dialysis Unit, Department of Woman, Child and Urological Diseases, Azienda Ospedaliero-Universitaria 'Sant'Orsola-Malpighi', Bologna, Italy. 5. Endocrinology Unit, Department of Woman, Child and Urological Diseases, Azienda Ospedaliero-Universitaria 'Sant'Orsola-Malpighi', Bologna, Italy. 6. Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland. 7. Chair and Clinical Department of Pediatrics, SMDZ in Zabrze, SUM in Katowice, Katowice, Poland. 8. Department of General Pediatrics, University Children's Hospital, Münster, Germany. 9. Department of Pediatrics, II University of Naples, Naples, Italy. 10. Department of Pediatric Nephrology, Collegium Medicum of the Jagiellonian University, Cracow, Poland. 11. Department of Pediatrics, Immunology and Nephrology, Polish Mothers Memorial Hospital Research Institute, Lódz, Poland. 12. Department of Pediatric Nephrology, Charité Universitätsmedizin Berlin, Charité Children's Hospital, Berlin, Germany. 13. Pediatric Nephrology, 'A. and P. Kyriakou' Children's Hospital, Athens, Greece. 14. Department of Pediatrics and Nephrology, Medical University of Bialystok, Bialystok, Poland. 15. Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland. 16. Department of Nephrology, Children's Hospital, Katowice, Poland. 17. Dialysis Center, District Hospital, Rzeszów, Poland. 18. Department of Pediatrics, Medical University of Gdansk, Nephrology and Hypertension, Gdansk, Poland. 19. Pediatric Nephrology, Hospital G.Brotzu, Cagliari, Italy. 20. Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 21. University Children's Hospital, Medical Faculty Skopje, Skopje, Macedonia. 22. Nephrology Department, University Children's Hospital, Belgrade, Serbia. 23. Division of Nephrology, University Children's Hospital, Ljubljana, Slovenia. 24. Mater Dei Hospital, Msida, Malta. 25. Department of Pediatric and Adolescent Medicine, Skåne University Hospital, Lund, Sweden. 26. Department of Pediatrics, Inje University Busan Paik Hospital, Busan, Korea. 27. Department of Pediatrics, Ajou University Daewoo Hospital, Geoje, Korea. 28. Department of Pediatrics, Ehwa University Mokdong Hospital, Seoul, Korea. 29. Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea. 30. Department of Pediatrics, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea. 31. Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland. 32. Laboratory of Histomorphology and Molecular Biology of the Kidney, Department of Medicine, University of Padova, Padova, Italy. 33. Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy. 34. Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. 35. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany. 36. University College London, Institute of Child Health and Great Ormond Street Hospital for Children, National Health Service Trust, London, UK.
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Background: 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. Methods: 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. Results: 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. Conclusions: 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: Marcin Zaniew; Małgorzata Mizerska-Wasiak; Iga Załuska-Leśniewska; Piotr Adamczyk; Katarzyna Kiliś-Pstrusińska; Adam Haliński; Jan Zawadzki; Beata S Lipska-Ziętkiewicz; Krzysztof Pawlaczyk; Przemysław Sikora; Michael Ludwig; Maria Szczepańska Journal: Int Urol Nephrol Date: 2017-08-16 Impact factor: 2.370
Authors: Sindhu Naik; Andrew R Wood; Maté Ongenaert; Paniz Saidiyan; Edo D Elstak; Henriëtte L Lanz; Jan Stallen; Richard Janssen; Elizabeth Smythe; Kai S Erdmann Journal: Int J Mol Sci Date: 2021-05-19 Impact factor: 5.923
Authors: Marine Berquez; Jonathan R Gadsby; Beatrice Paola Festa; Richard Butler; Stephen P Jackson; Valeria Berno; Alessandro Luciani; Olivier Devuyst; Jennifer L Gallop Journal: Kidney Int Date: 2020-09-09 Impact factor: 10.612