Clinical and genetic characteristics of Dent's disease type 1 in Europe

DENT study group, Carla Burballa, Gerard Cantero-Recasens, Larisa Prikhodina, Francesca Lugani, Karlpeter Schlingmann, Petr V. Ananin, Martine Besouw, Detlef Bockenhauer, Leire Madariaga, Aurelia Bertholet-Thomas, Francesca Taroni, Mattia Parolin, Peter Conlon, Francesco Emma, Dorella Del Prete, Dominique Chauveau, Linda Koster-Kamphuis, Marc Fila, Andrea PasiniIsabel Castro, Giacomo Colussi, Marta Gil, Barian Mohidin, Tanja Wlodkowski, Franz Schaefer, Gema Ariceta*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    5 Citaten (Scopus)
    21 Downloads (Pure)


    Background. Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis- nephrocalcinosis, progressive chronic kidney disease (CKD) and kidney failure (KF). Current management is symptomatic and does not prevent disease progression. Here we describe the contemporary DD1 picture across Europe to highlight its unmet needs. 

    Methods. A physician-based anonymous international e-survey supported by several European nephrology networks/societies was conducted. Questions focused on DD1 clinical features, diagnostic procedure and mutation spectra. 

    Results. A total of 207 DD1 male patients were reported; clinical data were available for 163 with confrmed CLCN5 mutations. Proteinuria was the most common manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithi- asis. After 5.5 years, ≈50% of patients presented with renal dysfunction, 20.7% developed CKD stage ≥3 and 11.1% developed KF. At the last visit, hypercalciuria was more frequent in paedi-atric patients than in adults (73.4% versus 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation, decreased glomerular fltration rate was more frequent in subjects with CLCN5 mutations afecting the pore or CBS domains compared with those with early-stop mutations. 

    Conclusions. Results from this large DD1 cohort confrm previous fndings and provide new insights regarding age and genotype impact on CKD progression. Our data strongly support that DD1 should be considered in male patients with CKD, nephrocalcinosis/hypercalciuria and non-nephrotic pro-teinuria and provide additional support for new research opportunities.

    Originele taal-2English
    Pagina's (van-tot)1497-1507
    Aantal pagina's11
    TijdschriftNephrology Dialysis Transplantation
    Nummer van het tijdschrift6
    StatusPublished - jun.-2023

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