Clinical and genetic characteristics of Dent's disease type 1 in Europe
Carla Burballa, Gerard Cantero-Recasens, Larisa Prikhodina, Francesca Lugani, Karl‐Peter Schlingmann, Petr V. Ananin, Martine Besouw, Detlef Böckenhauer, Leire Madariaga, Aurélia Bertholet‐Thomas, Francesca Taroni, Mattia Parolin, Peter J. Conlon, Francesco Emma, Dorella Del Prete, Dominique Chauveau, Linda Koster‐Kamphuis, Marc Fila, Andrea Pasini, Isabel Castro, Giacomo Colussi, Marta Gil, Barian Mohidin, Tanja Wlodkowski, Franz Schaefer, Gema Ariceta, for the DENT study group, Hopital Femme Mère Enfant, Justine Bacchetta, Fabio Paglialonga, Luisa Murer, Ilze Andersone, John A. Sayer, Olivia Boyer, Tanja Kersnik Levart, Rina Rus, Dušan Paripović, Esther Rubio Gonzalez, Francisco R. Nieto, Jakub Zieg, José Ángel Caballero, Julia Vara, Mandy G. Keijzer‐Veen, Pietro Manuel Ferraro, Ramón González, Ramon Maria Saracho Rotaeche, Roberta Fenoglio, Sandra Ballesteros, Serafin Tallon Lobo, Marie Sophie Ghuysen, Flor Ángel Ordóñez Álvarez, Maria Vandyck, Mai Rosenberg, Hjørdis Thorsteinsdottir, Velibor Tasić, Meral Torun Bayram, Sevgı Mır, George Claudiu Costea, Nurdan Yıldız, Javier Lumbreras, Sibel Yel, Rimantė Čerkauskienė, Angela La Manna, Elhussein A. Elhassan, Francesca Ciurli, Anna Meseguer, Mónica Durán
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.