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Long-term renal outcome in children with OCRL mutations : Retrospective analysis of a large international cohort

Zaniew, Marcin ; Bökenkamp, Arend ; Kołbuc, Marcin ; La Scola, Claudio ; Baronio, Federico ; Niemirska, Anna ; Szczepańska, Maria ; Bürger, Julia ; La Manna, Angela and Miklaszewska, Monika , et al. (2018) In Nephrology Dialysis Transplantation 33(1). p.85-94
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... (More)

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 (b0.46, 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chronic kidney disease, Dent-2 disease, Lowe syndrome, Nephrocalcinosis, OCRL
in
Nephrology Dialysis Transplantation
volume
33
issue
1
pages
10 pages
publisher
Oxford University Press
external identifiers
  • pmid:27708066
  • pmid:27708066
  • scopus:85040829008
ISSN
0931-0509
DOI
10.1093/ndt/gfw350
language
English
LU publication?
yes
id
3172fd6b-b169-4de1-a9e7-5f6f92ff26c2
date added to LUP
2018-02-06 12:52:38
date last changed
2025-02-18 07:57:20
@article{3172fd6b-b169-4de1-a9e7-5f6f92ff26c2,
  abstract     = {{<p>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 &lt; 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 &lt; 0.01). On multivariate analysis, eGFR was dependent only on age (b0.46, P &lt; 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.</p>}},
  author       = {{Zaniew, Marcin and Bökenkamp, Arend and Kołbuc, Marcin and La Scola, Claudio and Baronio, Federico and Niemirska, Anna and Szczepańska, Maria and Bürger, Julia and La Manna, Angela and Miklaszewska, Monika and Rogowska-Kalisz, Anna and Gellermann, Jutta and Zampetoglou, Argyroula and Wasilewska, Anna and Roszak, Magdalena and Moczko, Jerzy and Krzemień, Aleksandra and Runowski, Dariusz and Siteń, Grzegorz and Załuska-Leśniewska, Iga and Fonduli, Patrizia and Zurrida, Franca and Paglialonga, Fabio and Gucev, Zoran and Paripovic, Dusan and Rus, Rina and Said-Conti, Valerie and Sartz, Lisa and Chung, Woo Yeong and Park, Se Jin and Lee, Jung Won and Park, Yong Hoon and Ahn, Yo Han and Sikora, Przemysław and Stefanidis, Constantinos J. and Tasic, Velibor and Konrad, Martin and Anglani, Franca and Addis, Maria and Cheong, Hae Il and Ludwig, Michael and Bockenhauer, Detlef}},
  issn         = {{0931-0509}},
  keywords     = {{Chronic kidney disease; Dent-2 disease; Lowe syndrome; Nephrocalcinosis; OCRL}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  pages        = {{85--94}},
  publisher    = {{Oxford University Press}},
  series       = {{Nephrology Dialysis Transplantation}},
  title        = {{Long-term renal outcome in children with OCRL mutations : Retrospective analysis of a large international cohort}},
  url          = {{http://dx.doi.org/10.1093/ndt/gfw350}},
  doi          = {{10.1093/ndt/gfw350}},
  volume       = {{33}},
  year         = {{2018}},
}