Identification cohort: several plakins, complement-related proteins, and glycoproteins were more abundant in uEVs of ADPKD patients whereas annexin A2, contactin-1, syndecan-4, and granulins were less abundant in ADPKD patients.Confirmation cohort 1-3: the abundance of villin-1, envoplakin, periplakin, complement 3, and complement 9 was higher in uEVs of ADPKD patients. However, while complement was already increased in uEVs from ADPKD patients with intact kidney function, villin-1, periplakin, and envoplakin were only elevated in progressing CKD. Here, ANXA2 is linked to autosomal dominant polycystic kidney disease.