a. genetic diseases and molecular genetics

Nephrology Dialysis Transplantation 33 (Supplement 1): i346–i356, 2018 doi:10.1093/ndt/gfy104

A. GENETIC DISEASES AND MOLECULAR GENETICS

SP001 AUTOSOMAL DOMINANT TUBULOINTERSTITIAL KIDNEY DISEASE (ADTKD): A RARE BUT UNDERDIAGNOSED CAUSE OF END STAGE CHRONIC KIDNEY DISEASE Michele Battista2, Claudio Musetti2, Roberta Miglio2, Daniela Palmieri2, Mara Giordano1, Marco Quaglia2, Vincenzo Cantaluppi2 1 Department of Health Sciences and IRCAD, Laboratory of Genetics, University of Piemonte Orientale “Avogadro”, University Hospital "Maggiore della Carit a", Novara, Italy and 2Department of Translational Medicine, Nephrology and Kidney Transplant Unit, University of Piemonte Orientale “Avogadro”, University Hospital "Maggiore della Carita", Novara, Italy INTRODUCTION AND AIMS: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a new nosological entity which encompasses rare genetic nephropathies (ADTKD-UMOD, ADTKD-HNF1B, ADTKD-MUC1, ADTKD-REN) potentially leading to end-stage renal disease (ESRD). However, burden of disease and evolution are still not well defined. We herein retrospectively describe a monocentric series of ADTKD including patients referred to our centre for CKD, ESRD or kidney transplant (Ktx) over the last decade (2007 - 2017) METHODS: Genetic analyses were performed according to our institution procedures. In particular, genetic analysis for MUC1 mutation was performed by SNaPshot minisequencing, specifically designed to detect a single cytosine insertion in the MUC1VNTR; genetic analysis of UMOD gene mutations was performed on exons 3 and 4; genetic analysis of HNF1B gene mutations included the entire coding region of the HNF1B gene and intron-exon boundaries and search for deletions of the single exons and of the entire gene was performed by multiplex ligation-dependent probe amplification (MLPA assay) RESULTS: ADTKD was genetically diagnosed in 40 pts: 25/40 (62.5%) ADTKDUMOD (16 families; 11 with one tested proband and 5 with more than one tested members); 12/40 (30.0%) ADTKD-HNF1B (10 families; 9 with one tested proband and 1 with 3 tested members); 3/40 (7.5%) ADTKD-MUC1 (2 families, 1 with 2 tested members). Among them 12/40 (10/25 UMOD, 2/12 HNF1B) had normal kidney function at diagnosis (38.3618.3 yrs) and 28/40 (70%) developed CKD at 46.8618.1 yrs. ESRD developed in 20/28 (71.4%) at the age of 51.6 6 15.9 yrs and 7/20 patients (35%) were late diagnosis (already with ESRD). Overall 13 of these patients (32.5%), including 7/25 UMOD, 4/12 HNF1B and 2/3 MUC1, underwent KTx at 53.8 6 10.7 yrs. Patients with ADTKD-MUC1 developed ESRD with a higher incidence (p ¼ 0.033) and at a younger age (p ¼ 0.013) than probands with other forms of ADTKD. Overall ADTKD patients accounted for 1% of patients in our KTx cohort (n¼1100) and 4.0% of KTx recipients with an unknown diagnosis of causal nephropathy (n¼278) CONCLUSIONS: In conclusion, ADTKD is a rare but probably under-diagnosed cause of ESRD, particularly in uremic patients reaching a KTx program without a definite diagnosis of causal nephropathy. This entity should considered as a possible cause of ESRD especially in young (