ArticleJournal of the American Society of Nephrology : JASN2016
Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Mechanistic Target of Rapamycin Complex 1 in Distal Convoluted Tubule and Renal Potassium Handling.Journal of the American Society of Nephrology : JASN · 2025Article
- Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Mechanism of tacrolimus in the treatment of lupus nephritis.Frontiers in pharmacology · 2024Review
- Calcineurin inhibitors stimulate Kir4.1/Kir5.1 of the distal convoluted tubule to increase NaCl cotransporter.JCI insight · 2023Article
- The serine-threonine protein phosphatases that regulate the thiazide-sensitive NaCl cotransporter.Frontiers in physiology · 2023Review
- Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Molecular mechanisms for the modulation of blood pressure and potassium homeostasis by the distal convoluted tubule.EMBO molecular medicine · 2022Review
- Targeting Calcineurin Inhibitor-Induced Arterial Hypertension in Liver Transplanted Children Using Hydrochlorothiazide.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2022Article
- Roles of WNK4 and SPAK in KAmerican journal of physiology. Renal physiology · 2021Article
- Etiology and management of hypertension in patients with cancer.Cardio-oncology (London, England) · 2021Review
- NaCl cotransporter activity and MgAmerican journal of physiology. Renal physiology · 2020Review
- Review
- Sodium-calcium exchanger 1 is the key molecule for urinary potassium excretion against acute hyperkalemia.PloS one · 2020Article
- The Many Faces of Calcineurin Inhibitor Toxicity-What the FK?Advances in chronic kidney disease · 2020Review
- Tacrolimus-induced hypomagnesemia and hypercalciuria requires FKBP12 suggesting a role for calcineurin.Physiological reports · 2020Article
- Clinical importance of potassium intake and molecular mechanism of potassium regulation.Clinical and experimental nephrology · 2019Review
- Intracellular chloride: a regulator of transepithelial transport in the distal nephron.Current opinion in nephrology and hypertension · 2019Review
- 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
- Zinc deficiency induces hypertension by promoting renal NaAmerican journal of physiology. Renal physiology · 2019Article
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Authors and funding
10 authors.
Funding
Abstract
Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruption alone did not cause phenotypic effects. When treated with tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice. Mice lacking FKBP12 along the nephron also maintained a normal relationship between plasma potassium levels and the abundance of phosphorylated NCC with tacrolimus treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC. Together, these results suggest that tacrolimus causes hypertension predominantly by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide diuretics may be particularly effective for lowering BP in tacrolimus-treated patients with hypertension.
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