ESPN 53rd Annual Meeting

ESPN 2021


 
Clinical features and management of Dent’s Disease type 1 (DD1) in Europe
CARLA BURBALLA 1 LARISA PRIKHODINA 2 FRANCESCA LUGANI 3 KARLPETER SCHLINGMANN 4 PETR V ANANIN 5 DETLEF BOCKENHAUER 6 LEIRE MADARIAGA 7 AURELIA BERTHOLET-THOMAS 8 FRANCESCA TARONI 9 DORELLA DELPRETE 10 DOMINIQUE CHAUVEAU 11 MATTIA PAROLIN 12 MARC FILA 13 ANDREA PASINI 14 LINDA KOSTER-KAMPHUIS 15 ISABEL CASTRO 16 BARIAN MOHIDIN 1 GIACOMO COLUSSI 17 MARTA GIL 18 GEMA ARICETA 1

1- VALL DHEBRON HOSPITAL_ VALL DHEBRON RESEARCH INSTITUTE (VHIR), BARCELONA, SPAIN
2- RESEARCH & CLINICAL INSTITUTE FOR PEDIATRICS, PIROGOV, RUSSIA
3- ISTITUTO G. GASLINI, GENOVA, ITALY
4- UNIVERSITY CHILDRENS HOSPITAL, MÜNSTER, GERMANY
5- SCIENTIFIC CENTRE OF CHILDREN HEALTH 2, MOSCOW, RUSSIA
6- GREAT HORMOND STREET HOSPITAL, LONDON, UNITED KINGDOM
7- HOSPITAL DE CRUCES, BILBAO, SPAIN
8- HOPITAL FEMME MERE ENFANT, LYON, FRANCE
9- POLICLINICO IRCCS ,MILAN, ITALY
10- AZIENDA OSPEDALE-UNIVERSITA, PADOVA, ITALY
11- HOPITAL RANGUEIL, TOULOUSE, FRANCE
12- AZIENDA OSPEDALIERA, PADOVA, ITALY
13- ARNAUD DE VILLENEUVE, MONTPELLIER, FRANCE
14- AZIENDA OSPEDALIERO-UNIVERSITARIA SANTORSOLA-MALPIGHI BOLOGNA, ITALY
15- RADBOUDUMC AMALIA CHILDRENS HOSPITAL, NIJMEGEN, THE NETHERLANDS
16- COMPLEXO HOSPITALARIO DE PONTEVEDRA, PONTEVEDRA, SPAIN
17- NIGUARDA HOSPITAL, MILAN, ITALY
18- HOSPITAL UNIVERSITARIO SANTIAGO DE COMPOSTELA, SANTIAGO DE COMPOSTELA, SPAIN
 
Introduction:

Dent’s disease type 1 (DD1) is a rare X-linked nephropathy characterized by proximal tubule dysfunction, including low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis, nephrocalcinosis and often progressive renal failure (RF). A broad phenotypic variability has been reported, with no genotype-phenotype relationship and limited long-term knowledge. The prevalence of DD1 is unknown. Geographic dispersion of the few diagnosed cases makes epidemiologic and clinical studies difficult.

Material and methods:

A physician-based anonymous survey supported by ERKNet, ESPN and ERA-EDTA, either distributed via post mail or e-mail, was conducted. Questions were aimed to assess the prevalence and disease traits in the target population.

Results:

73 nephrologist from 63 hospitals in 22 European countries participated in this survey. 230 patients with DD1 were reported. Demographic and clinical data were available for 152 male patients with confirmed mutations in CLCN5 gene. Median age at diagnosis was 6 years [IQR,2.5-12] and the main sign leading to diagnosis was proteinuria (see Figure 1); 11.5% had positive family history. All patients showed LMWP, 66.9% nephrocalcinosis, 44.4% hypercalciuria and 25.6% kidney stones. 60% patients had progressed to chronic kidney disease with estimated glomerular filtrataion (eGFR) <90 ml/min at last follow-up. Eight patients presented RF at 35 years [IQR,30-43]. Patients < 18 years at last follow-up showed hypercalciuria more frequently than those older (51.4% vs. 22.7%; p<0.001), less glycosuria (8.9 % vs. 43.2%; p<0.01) and better eGFR (90 ml/min [IQR,72-120] vs. 58 ml/min [IQR,18-101]).

Conclusions:

Large registries are important to increase the knowledge of this probably under-diagnosed disease. LMWP, the hallmark of DD1, should be measure in males with proteinuria, nephrocalcinosis, lithiasis or bone disease although the phenotype is very variable and evolves with age and loss eGFR. Our results confirm DD1 manifestations described in smaller cohorts and show long-term outcomes with less percentatge of renal failure.