NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity

摘要: Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate thiazide-sensitive NaCl cotransporter (NCC). A common side effect of CNIs is hypertension. Renal salt transporters such as NCC are excreted in urinary extracellular vesicles (uEVs) after internalization into multivesicular bodies. Human indicate also increase abundance uEVs, but results conflicting no relationship with function has been shown. Therefore, we investigated effects CsA Tac on both total (tNCC) phosphorylated at Thr60 phosphorylation site (pNCC) assessed whether uEVs predicts blood pressure response to thiazide diuretics. Our show kidney transplant recipients treated (n = 9) or 23), tNCC pNCC 4-5 fold higher than CNI-free 13) healthy volunteers 6). In hypertensive recipients, abundances prior treatment thiazides predicted thiazides. During treatment, increased responders 10), markedly decreased non-responders 8). Thus, our these increases correlate This implies assessment could represent an alternate method guide anti-hypertensive therapy recipients.