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. 2023 May 31;38(6):1497-1507.
doi: 10.1093/ndt/gfac310.

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

Carla Burballa  1 , Gerard Cantero-Recasens  1 , Larisa Prikhodina  2 , Francesca Lugani  3 , Karlpeter Schlingmann  4 , Petr V Ananin  5 , Martine Besouw  6 , Detlef Bockenhauer  7 , Leire Madariaga  8 , Aurelia Bertholet-Thomas  9 , Francesca Taroni  10 , Mattia Parolin  11 , Peter Conlon  12 , Francesco Emma  13 , Dorella Del Prete  14 , Dominique Chauveau  15 , Linda Koster-Kamphuis  16 , Marc Fila  17 , Andrea Pasini  18 , Isabel Castro  19 , Giacomo Colussi  20 , Marta Gil  21 , Barian Mohidin  22 , Tanja Wlodkowski  23 , Franz Schaefer  23 , Gema Ariceta  1 ; DENT study group
Collaborators, Affiliations

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

Carla Burballa et al. Nephrol Dial Transplant. .

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 spectra.

Results: A total of 207 DD1 male patients were reported; clinical data were available for 163 with confirmed 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% nephrolithiasis. 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 paediatric 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 filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared with 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.

Keywords: CLCN5 gene; Dent's disease 1 (DD1); low molecular weight proteinuria; nephrocalcinosis; tubulopathy.

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