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

Burballa, Carla; Cantero-Recasens, Gerard; Prikhodina, Larisa; Lugani, Francesca; Schlingmann, Karlpeter; Ananin, Petr V; Besouw, Martine; ... DENT study group; + view all (2023) Clinical and genetic characteristics of Dent's Disease type 1 in Europe. Nephrology Dialysis Transplantation , 38 (6) pp. 1497-1507. 10.1093/ndt/gfac310. Green open access

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Abstract

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 spectrum. RESULTS: Two-hundred seven DD1 male patients were reported, being clinical data available for 163 with confirmed CLCN5 mutations. Proteinuria was the most common leading manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithiasis. After 5.5 years, ∼50% of patients presented renal dysfunction, 20.7% developed CKD ≥ 3, and 11.1% KF. At last visit, hypercalciuria was more frequent in pediatric patients than in adults (73.4% vs. 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation was observed, decreased glomerular filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared to those with early-stop mutations. CONCLUSIONS: Results from this large DD1 cohort confirm previous findings 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 proteinuria and provide additional support for new research opportunities.

Type: Article
Title: Clinical and genetic characteristics of Dent's Disease type 1 in Europe
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ndt/gfac310
Publisher version: https://doi.org/10.1093/ndt/gfac310
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: clcn5 gene, dent's disease 1 (dd1), low-molecular-weight-proteinuria, nephrocalcinosis, tubulopathy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10166230
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