#5542 THE ITALIAN REGISTRY OF POLYCYSTIC KIDNEY DISEASE (RIRP): DESIGN, PATIENT CHARACTERISTICS AND INITIAL RESULTS
Authors: Cortinovis Roberta , Dordoni Chiara , Mescia Federica , Mazza Cinzia , Rigato Matteo , Corradi Valentina , Aucella Filippo , Melchionda Salvatore , Zacchia Miriam , Gesualdo Loreto , DI Bari Ighli , Galliani Marco , Pani Antonello , Capelli Irene , Stallone Giovanni , Guarneri Marco , Magistroni Riccardo , Giunta Rosa , Cupisti Adamasco , Bellizzi Vincenzo , Monardo Paolo , Tamagnone Michela , Pisani Isabella , Castellano Giuseppe , Cirami Calogero , DI Liberato Lorenzo , Papalia Giuliana , Alberici Federico , Scolari Francesco , Izzi Claudia 
Published: June 2023

Abstract

Background and Aims
ADPKD is the most common form of inherited renal disease worldwide. ADPKD care has advanced over the past decade by the identification of several clinical/genetic risk factors of progression and approval of first disease-modifying drug. Further clinical outcomes research is needed to improve patient-centered clinical care; in addition new disease-modifying therapies are in pipeline, requiring a growing need for patient enrolment in clinical trials. To advance these goals, the Italian Society of Nephrology, supported by the Italian PKD Foundation (AIRP) established in 2020 the creation of a National web-based ADPKD Registry. Here we present the design of this Registry and the preliminary results.

Method
Adult patients with clinical or genetically confirmed diagnosis of ADPKD have been enrolled in the Registry, hosted by a secure online platform including both a clinical and genetic database. Databases have modular design collecting clinical features, including demographic data, type of diagnosis, e-GFR at onset and at time of first and last nephrological referral, age at onset of hypertension (HTN) and major urological complications (UC), Total Kidney Volume (hTKV) and Mayo Imaging Classification of ADPKD, age at ESRD, use of aspecific renal-protective and disease-modifying drugs, additional risk factors for CKD progression (smoke, diabetes, NSAID), extra-renal manifestations. Genetic data collected include type of PKD1/2 variant with ACMG classification and pathogenic prediction tools, testing method, results of segregation analysis. Statistics included estimation of eGFR slope using linear-mixed modelling.

Results
By January 2023, the Registry had recruited 985 ADPKD patients across 21 Italian Nephrology Unit; 513 (52,1%) were females; 967 (98,2%) Caucasians. Familiar history of ADPKD was reported in 738 patients (79%). All CKD stages were represented and 105 (14,1%) patients reached ESRD (median age 57y ± 11,5). hTKV was available for 353 (35,9%) patients, with a median value of 1100 ± 996 ml/m; a Mayo class of 1C or higher was found in 221 (70,4%). PROPKD score was evaluated in 162 patients, and in 50% of them it was associated with low risk of progression. A total of 191 (21,6%) were receiving Tolvaptan. Demographic and clinical characteristics are summarized in Table 1.
Genetic testing was performed in 288 patients; 111 (38,5%) had PKD1 truncating (T) variants; 67 (23,3%) PKD1 non truncating variants; 69 (24%) PKD2 variants. In 41 patients (14,2%) no pathogenic variants were detected.
In our cohort deterioration of renal function over time, estimated using eGFR slope was significantly associated with Mayo Imaging classes, high-medium PROPKD score, PKD1-T variant, HTN onset before 35 yo (Figure) and early UC (−2,3 vs. −1,9 ml/min/1.73m2/y, p = 0.014).

Conclusion
The Italian ADPKD National Registry is an important research tool collecting clinical and genetic information. Our preliminary data confirm that in the Italian population genotype, early onset HTN or UC, Mayo Imaging classification and PROPKD score are able to predict deterioration of GFR in ADPKD. The future empowerment of the Registry will provide a comprehensive description of clinical features and genetic variants related to ADPKD in a large cohort of Italian patients, enabling us to better understand genotype-phenotype correlation. Furthermore, the Registry could be an opportunity to identify patients suitable for future clinical trials or observational studies concerning specific aspects of the disease.