Autosomal dominant polycystic kidney disease in Italy

Background and Hypothesis Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disorder, is primarily caused by pathogenic variants in PKD1 and PKD2. Although the natural history of ADPKD has been extensively characterized, real-world studies integrating clinical, imaging, and genetic data remain limited. In 2020, the Italian ADPKD Registry was established to describe disease presentation, identify prognostic factors, and evaluate contemporary management of ADPKD across Italy. Methods Italian ADPKD registry is a nationwide, multicentre observational study involving 23 nephrology and genetic centres. Clinical, imaging, and genetic (PKD1/PKD2) data from adults enrolled through June 2025 were analysed. Prognostic assessment included genotype, Mayo Imaging Classification (MIC), PROPKD score, kidney failure (KF) and longitudinal estimated glomerular filtration rate trajectories. Results Overall, 1771 participants were included (52.8% women; median age 50.3 years). Genetic testing was performed in 864 patients, identifying pathogenic or likely pathogenic variants in 666 (77.1%): 471 (70.7) in PKD1 and 195 (29.3%) in PKD2. Hypertension and chronic kidney pain were found in 75.7% and in 34.3% of patients, respectively. Intracranial aneurysms occurred in 8.7% of patients. Tolvaptan was used in 310/1670 patients (18.6%). KF occurred in 15.7% of patients, at a median age 55.3 years. PKD1 truncating variants, early-onset hypertension, major urological complications, higher MIC and higher PROPKD scores were associated with poorer kidney outcomes. Conclusion The Italian ADPKD Registry provides a large nationwide real-world characterization of contemporary ADPKD care. Established clinical, imaging, and genetic markers were associated with disease severity and kidney outcomes. Imaging-based risk stratification and disease-modifying therapy have been incorporated into routine clinical practice, although their uptake remains incomplete; however, access to genetic testing is heterogeneous across centres. The Registry provides an infrastructure for longitudinal evaluation of disease progression and treatment strategies.