Reduced urinary release of AQP1‐ and AQP2‐bearing extracellular vesicles in patients with advanced chronic kidney disease

Abstract Although several studies have shown that release of water channel proteins, aquaporin 1 (AQP1) and AQP2 in urinary extracellular vesicles (uEV‐AQP1 and ‐AQP2), were altered in experimental kidney injury models, their release in human chronic kidney disease (CKD) has been largely unexplored. The aim of the present study was to clarify whether the release of uEV‐AQP1 and ‐AQP2 is altered in patients with CKD. Urine samples were collected from 15 healthy volunteers (normal group) and 62 CKD patients who were categorized into six glomerular filtration rate (GFR) categories (G1, G2, G3a, G3b, G4, and G5) in between 2005 and 2016 at Miyazaki Prefectural Miyazaki Hospital, Japan. uEV‐proteins were evaluated by immunoblot analysis. The release of AQP1 and AQP2 were significantly decreased in patients with both CKD G4 and G5, in comparison with the normal group. The area under the receiver operating characteristic (ROC) curve (AUC) values for AQP1 and AQP2 in patients with CKD G4 and G5 were 0.926 and 0.881, respectively. On the other hand, the AUC values in patients with CKD G1‐G3 were 0.512 for AQP1 and 0.680 for AQP2. Multiple logistic regression analysis showed that AQP1 and AQP2 in combination were useful for detecting CKD G4 and G5, with a higher AUC value of 0.945. These results suggest that the release of uEV‐AQP1 and ‐AQP2 was decreased in patients with CKD G4 and G5, and these proteins might be helpful to detect advanced CKD.