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
N1 - Publisher Copyright:
© The Author 2017.
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
UR - http://www.scopus.com/inward/record.url?scp=85040829008&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfw350
DO - 10.1093/ndt/gfw350
M3 - Article
C2 - 27708066
AN - SCOPUS:85040829008
SN - 0931-0509
VL - 33
SP - 85
EP - 94
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 1
ER -