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

Marcin Zaniew, Arend Bökenkamp, Marcin Kołbuc, Claudio La Scola, Federico Baronio, Anna Niemirska, Maria Szczepańska, Julia Bürger, Angela La Manna, Monika Miklaszewska, Anna Rogowska-Kalisz, Jutta Gellermann, Argyroula Zampetoglou, Anna Wasilewska, Magdalena Roszak, Jerzy Moczko, Aleksandra Krzemień, Dariusz Runowski, Grzegorz Siteń, Iga Załuska-LeśniewskaPatrizia Fonduli, Franca Zurrida, Fabio Paglialonga, Zoran Gucev, Dusan Paripovic, Rina Rus, Valerie Said-Conti, Lisa Sartz, Woo Yeong Chung, Se Jin Park, Jung Won Lee, Yong Hoon Park, Yo Han Ahn, Przemysław Sikora, Constantinos J. Stefanidis, Velibor Tasic, Martin Konrad, Franca Anglani, Maria Addis, Hae Il Cheong, Michael Ludwig, Detlef Bockenhauer

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalNephrology Dialysis Transplantation
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Chronic Renal Insufficiency
Oculocerebrorenal Syndrome
Kidney
Mutation
Glomerular Filtration Rate
Nephrocalcinosis
Disease Progression
Survival Analysis
Proteinuria
Hypercalciuria
Multivariate Analysis
Genotype
Phenotype

Keywords

  • Chronic kidney disease
  • Dent-2 disease
  • Lowe syndrome
  • Nephrocalcinosis
  • OCRL

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Zaniew, M., Bökenkamp, A., Kołbuc, M., La Scola, C., Baronio, F., Niemirska, A., ... Bockenhauer, D. (2018). Long-term renal outcome in children with OCRL mutations: Retrospective analysis of a large international cohort. Nephrology Dialysis Transplantation, 33(1), 85-94. https://doi.org/10.1093/ndt/gfw350

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; Miklaszewska, Monika; Rogowska-Kalisz, Anna; Gellermann, Jutta; Zampetoglou, Argyroula; Wasilewska, Anna; Roszak, Magdalena; Moczko, Jerzy; Krzemień, Aleksandra; Runowski, Dariusz; Siteń, Grzegorz; Załuska-Leśniewska, Iga; Fonduli, Patrizia; Zurrida, Franca; Paglialonga, Fabio; Gucev, Zoran; Paripovic, Dusan; Rus, Rina; Said-Conti, Valerie; Sartz, Lisa; Chung, Woo Yeong; Park, Se Jin; Lee, Jung Won; Park, Yong Hoon; Ahn, Yo Han; Sikora, Przemysław; Stefanidis, Constantinos J.; Tasic, Velibor; Konrad, Martin; Anglani, Franca; Addis, Maria; Cheong, Hae Il; Ludwig, Michael; Bockenhauer, Detlef.

In: Nephrology Dialysis Transplantation, Vol. 33, No. 1, 01.01.2018, p. 85-94.

Research output: Contribution to journalArticle

Zaniew, M, Bökenkamp, A, Kołbuc, M, La Scola, C, Baronio, F, Niemirska, A, Szczepańska, M, Bürger, J, La Manna, A, Miklaszewska, M, Rogowska-Kalisz, A, Gellermann, J, Zampetoglou, A, Wasilewska, A, Roszak, M, Moczko, J, Krzemień, A, Runowski, D, Siteń, G, Załuska-Leśniewska, I, Fonduli, P, Zurrida, F, Paglialonga, F, Gucev, Z, Paripovic, D, Rus, R, Said-Conti, V, Sartz, L, Chung, WY, Park, SJ, Lee, JW, Park, YH, Ahn, YH, Sikora, P, Stefanidis, CJ, Tasic, V, Konrad, M, Anglani, F, Addis, M, Cheong, HI, Ludwig, M & Bockenhauer, D 2018, 'Long-term renal outcome in children with OCRL mutations: Retrospective analysis of a large international cohort', Nephrology Dialysis Transplantation, vol. 33, no. 1, pp. 85-94. https://doi.org/10.1093/ndt/gfw350
Zaniew, Marcin ; Bökenkamp, Arend ; Kołbuc, Marcin ; La Scola, Claudio ; Baronio, Federico ; Niemirska, Anna ; Szczepańska, Maria ; Bürger, Julia ; La Manna, Angela ; Miklaszewska, Monika ; Rogowska-Kalisz, Anna ; Gellermann, Jutta ; Zampetoglou, Argyroula ; Wasilewska, Anna ; Roszak, Magdalena ; Moczko, Jerzy ; Krzemień, Aleksandra ; Runowski, Dariusz ; Siteń, Grzegorz ; Załuska-Leśniewska, Iga ; Fonduli, Patrizia ; Zurrida, Franca ; Paglialonga, Fabio ; Gucev, Zoran ; Paripovic, Dusan ; Rus, Rina ; Said-Conti, Valerie ; Sartz, Lisa ; Chung, Woo Yeong ; Park, Se Jin ; Lee, Jung Won ; Park, Yong Hoon ; Ahn, Yo Han ; Sikora, Przemysław ; Stefanidis, Constantinos J. ; Tasic, Velibor ; Konrad, Martin ; Anglani, Franca ; Addis, Maria ; Cheong, Hae Il ; Ludwig, Michael ; Bockenhauer, Detlef. / Long-term renal outcome in children with OCRL mutations : Retrospective analysis of a large international cohort. In: Nephrology Dialysis Transplantation. 2018 ; Vol. 33, No. 1. pp. 85-94.
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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 (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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TY - JOUR

T1 - Long-term renal outcome in children with OCRL mutations

T2 - Retrospective analysis of a large international cohort

AU - Zaniew, Marcin

AU - Bökenkamp, Arend

AU - Kołbuc, Marcin

AU - La Scola, Claudio

AU - Baronio, Federico

AU - Niemirska, Anna

AU - Szczepańska, Maria

AU - Bürger, Julia

AU - La Manna, Angela

AU - Miklaszewska, Monika

AU - Rogowska-Kalisz, Anna

AU - Gellermann, Jutta

AU - Zampetoglou, Argyroula

AU - Wasilewska, Anna

AU - Roszak, Magdalena

AU - Moczko, Jerzy

AU - Krzemień, Aleksandra

AU - Runowski, Dariusz

AU - Siteń, Grzegorz

AU - Załuska-Leśniewska, Iga

AU - Fonduli, Patrizia

AU - Zurrida, Franca

AU - Paglialonga, Fabio

AU - Gucev, Zoran

AU - Paripovic, Dusan

AU - Rus, Rina

AU - Said-Conti, Valerie

AU - Sartz, Lisa

AU - Chung, Woo Yeong

AU - Park, Se Jin

AU - Lee, Jung Won

AU - Park, Yong Hoon

AU - Ahn, Yo Han

AU - Sikora, Przemysław

AU - Stefanidis, Constantinos J.

AU - Tasic, Velibor

AU - Konrad, Martin

AU - Anglani, Franca

AU - Addis, Maria

AU - Cheong, Hae Il

AU - Ludwig, Michael

AU - Bockenhauer, Detlef

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Dent-2 disease

KW - Lowe syndrome

KW - Nephrocalcinosis

KW - OCRL

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