#5496 EVALUATION OF THE PREDICTIVE ABILITY AND CONCORDANCE OF PROGNOSTIC SCORES FOR RAPID PROGRESSION IN ADPKD: A MULTICENTER COHORT
Authors: Aiello Valeria , Elhassan Elhussein , Cristalli Carlotta , Minicucci Andreina , Vella Anna , Ciurli Francesca , Montanari Francesca , Conti Amalia , Benson Katherine , Seri Marco , Sciascia Nicola , Schönauer Ria Anne-Rose , Halbritter Jan , La Manna Gaetano , Conlon Peter , Capelli Irene 
Published: June 2023

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of end-stage kidney disease (ESKD). It is characterized by the progressive development of bilateral renal cysts, resulting in enlargement of the kidney volume, hypertension (HBP), and ESKD. Recently, a position statement of the ERK-NET was published to assess indications for Tolvaptan according to 3 algorithmic criteria: total kidney volume (HtTKV) and Mayo Clinic Imaging Class (MCIC), rate of decline in eGFR, and the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score, combining clinical and genetic variables. In this scenario, these scores (MCIC and PROPKD) are alternatively used to define rapid progressor patients. In this retrospective multicentric cohort, the primary outcome was to evaluate and improve the concordance of sensitivity and specificity of MCIC and PROPKD predictive abilities for rapid disease progression.

Method
Data from adult ADPKD patients were obtained from 3 different renal centers (Bologna, Dublin, Berlin/Leipzig). We defined rapid disease progression as individuals with eGFR slope ≥3 mL/min/1.73m2/ yearly over 4 years (Clinical Score), or MCIC classes 1C-D-E (Imaging Score), or high-risk PROPKD score (7 to 9 points). Descriptive statistics were used to summarize clinical parameters. The concordance between MCIC and PROPKD was assessed using Kappa statistics. In individuals with PKD1 missense variants, the REVEL score was obtained and treated as a continuous variable; score greater than 0.65 were considered ‘pathogenic’ and regarded as PKD1-truncating variants for PROPKD score calculation.

Results
We evaluated 298 ADPKD patients, demographic and clinical data are summarized in Table 1. After 4 yr of follow-up, MCIC (p 0,041), HBP (p 0,031), and urological events (p &lt;0.001) result were statistically significant on multivariate analysis (Table 1). Assessment of rapid disease progression using PROPKD and MCIC scores yielded Kappa Cohen of 0,149; 47.9% (n = 143) were concordant, 49,32% (n = 148) patients identified as rapid progressor (RP) for MCIC were non- RP for PROPKD, while 2.3% (n = 7) of PROPKD score considered RP using PROPKD score were considered non-RP using MCIC classes. Following the reclassification of PKD1 missense variants by REVEL score, K of Cohen improved to 0.174, and PROPKD becomes predictive of fast progression also at multivariate (p 0.010).

Conclusion
Concordance between scores results low (K of Cohen 0,149). The PROPKD is more selective compared to the Mayo. Nevertheless, PROPKD allows the identification of some rapid progressor patients excluded from using the Mayo score only. The combined use of scoring may increase the ability to identify progressive patients. REVEL score could improve the agreement.