THE EVOLUTION OF THE RENAL FUNCTION IN A COHORT OF ITALIAN PATIENTS WITH ADPKD: AN ANALYSIS BY THE JOINT MODEL

Abstract Background and Aims The natural history of ADPKD has been defined in numerous studies in various countries and in various genetic and environmental contexts but the problem has not yet been studied in sufficiently large studies in the Italian population. We have studied the evolution of ADPKD in a cohort of 445 incident patients enrolled in a time span between 2012 and 2016 in 28 nephrological centers in 3 regions of central Italy. The main demographic and clinical characteristics of this cohort are reported below. [GRAPHICS] Method The analysis was carried out on a sample of 296 patients with at least 2 creatinine measurements prior to ESKD and with eGFR at onset ≥45 ml/min/1.73m2. The median follow-up was 15 years (range 1-42 years). The analysis of the data was carried out with the Joint model, an approach that allows the simultaneous modeling of longitudinal (repeated over time) and time to event ESKD or GFR<45 ml/min/1.73m2 data. This approach produces two sub-models: a longitudinal model (mixed linear model, sub-model A in the table) and a time to event model (Cox model, survival sub-model B in the Table). The two models are mutually associated through an analytical structure that quantifies the relationship between the variables of interest. [GRAPHICS] [GRAPHICS] Results The average eGFR decline in the entire population was -2.13 ml/min/1.73m2/year. In males the decline in GFR was significantly higher than in females (M: -2.63 ml/min/1.73m2; in F -1.74 ml/min/1.73m2/year, p <0.005) while it was not significant differences are observed for the different age groups considered separately in the two sexes (p = 0.158 in the M; p = 0.625 in the F). In the longitudinal model the age at diagnosis >30 years and the presence of hypertension were significantly associated with an accelerated decline in GFR and patients older than 50 years exhibited a reduction by 35 ml/min/1.73m2 greater than those younger than 30 years. In the survival model the GFR trend and sex were associated with the risk of renal survival. For each incremental baseline unit of GFR the risk for ESKD decreased by 16% (HR: 0.84) and in females the risk was about one third compared to males (HR: 0.31). Conclusion This study, the first to apply the joint model in the analysis of the evolution of renal function in ADPKD and the first in a sizeable cohort in Italy, provides important information on the progression of polycystic kidney disease in an incident series of Italian patients with ADPKD.