ArticlePloS one2017
NaCl cotransporter abundance in urinary vesicles is increased by calcineurin inhibitors and predicts thiazide sensitivity.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Urinary extracellular vesicles and tubular transport.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Review
- Urine Cell Transcriptomes Implicate Specific Renal Inflammatory Pathways Associated With Difficult-to-Control Hypertension.Journal of the American Heart Association · 2023Article
- The serine-threonine protein phosphatases that regulate the thiazide-sensitive NaCl cotransporter.Frontiers in physiology · 2023Review
- Molecular immune monitoring in kidney transplant rejection: a state-of-the-art review.Frontiers in immunology · 2023Review
- Molecular Mechanisms of Na-Cl Cotransporter in Relation to Hypertension in Chronic Kidney Disease.International journal of molecular sciences · 2022Review
- Does the composition of urinary extracellular vesicles reflect the abundance of renal NaPflugers Archiv : European journal of physiology · 2022Article
- Using human urinary extracellular vesicles to study physiological and pathophysiological states and regulation of the sodium chloride cotransporter.Frontiers in endocrinology · 2022Review
- Importance of extracellular vesicles in hypertension.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Extracellular Vesicles in Essential Hypertension: Hidden Messengers.Current hypertension reports · 2020Review
- The Many Faces of Calcineurin Inhibitor Toxicity-What the FK?Advances in chronic kidney disease · 2020Review
- The Demystification of Secondary Hypertension: Diagnostic Strategies and Treatment Algorithms.Current treatment options in cardiovascular medicine · 2019Review
- Urinary peptidomic biomarkers of renal function in heart transplant recipients.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019Article
- The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway.Journal of human hypertension · 2019Review
- Calcineurin dephosphorylates Kelch-like 3, reversing phosphorylation by angiotensin II and regulating renal electrolyte handling.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of the alternative splice variant of NCC in blood pressure control.Channels (Austin, Tex.) · 2018Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Animal studies have shown that the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus can activate the 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 studies indicate that CNIs also increase NCC abundance in uEVs, but results are conflicting and no relationship with NCC function has been shown. Therefore, we investigated the effects of CsA and Tac on the abundance of both total NCC (tNCC) and phosphorylated NCC at Thr60 phosphorylation site (pNCC) in uEVs, and assessed whether NCC abundance in uEVs predicts the blood pressure response to thiazide diuretics. Our results show that in kidney transplant recipients treated with cyclosporine (n = 9) or tacrolimus (n = 23), the abundance of both tNCC and pNCC in uEVs is 4-5 fold higher than in CNI-free kidney transplant recipients (n = 13) or healthy volunteers (n = 6). In hypertensive kidney transplant recipients, higher abundances of tNCC and pNCC prior to treatment with thiazides predicted the blood pressure response to thiazides. During thiazide treatment, the abundance of pNCC in uEVs increased in responders (n = 10), but markedly decreased in non-responders (n = 8). Thus, our results show that CNIs increase the abundance of both tNCC and pNCC in uEVs, and these increases correlate with the blood pressure response to thiazides. This implies that assessment of NCC in uEVs could represent an alternate method to guide anti-hypertensive therapy in kidney transplant recipients.
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Registered trials
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