ArticleAmerican journal of physiology. Renal physiology2017
Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms.
Article in American journal of physiology. Renal physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Development of conditional-siRNA programmable riboswitch for targeting adverse cardiac remodeling.Molecular therapy. Nucleic acids · 2025Article
- A comparative analysis of drug-induced kidney injury adverse reactions between cyclosporine and tacrolimus based on the FAERS database.BMC immunology · 2025Article
- TNF inhibits NKCC2 phosphorylation by a calcineurin-dependent pathway.American journal of physiology. Renal physiology · 2025Article
- Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism.Circulation research · 2024Article
- Role of calcineurin in regulating renal potassium (KActa physiologica (Oxford, England) · 2024Review
- Tubular deficiency of ABCA1 augments cholesterol- and NaAmerican journal of physiology. Renal physiology · 2024Article
- Cyclosporin-induced hypertension is associated with the up-regulation of Na+-K+-2Cl- cotransporter (NKCC2).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Kidney and blood pressure regulation-latest evidence for molecular mechanisms.Clinical kidney journal · 2023Review
- Calcineurin inhibitors stimulate Kir4.1/Kir5.1 of the distal convoluted tubule to increase NaCl cotransporter.JCI insight · 2023Article
- Blood pressure effects of sodium transport along the distal nephron.Kidney international · 2022Review
- Nephroprotective effects of Candesartan Cilexetil against Cyclosporine A-induced nephrotoxicity in a rat model.Journal of medicine and life · 2022Article
- Old and New Calcineurin Inhibitors in Lupus Nephritis.Journal of clinical medicine · 2021Review
- A five amino acids deletion in NKCC2 of C57BL/6 mice affects analysis of NKCC2 phosphorylation but does not impact kidney function.Acta physiologica (Oxford, England) · 2021Article
- Review
- Identifying New Substrates and Functions for an Old Enzyme: Calcineurin.Cold Spring Harbor perspectives in biology · 2020Review
- 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
- Prevention of complications from use of conventional immunosuppressants: a critical review.Journal of nephrology · 2019Review
- Arginine Vasopressin and Posterior Reversible Encephalopathy Syndrome Pathophysiology: the Missing Link?Molecular neurobiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Calcineurin dephosphorylates nuclear factor of activated T cells transcription factors, thereby facilitating T cell-mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation but may cause side effects, including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA). An involvement of major hormones like angiotensin II or arginine vasopressin (AVP) has been proposed. To resolve this issue, the effects of CsA treatment in normal Wistar rats, AVP-deficient Brattleboro rats, and cultured renal epithelial cells endogenously expressing either NKCC2 or NCC were studied. Acute administration of CsA to Wistar rats rapidly augmented phosphorylation levels of NKCC2, NCC, and their activating kinases suggesting intraepithelial activating effects. Chronic CsA administration caused salt retention and hypertension, along with stimulation of renin and suppression of renal cyclooxygenase 2, pointing to a contribution of endocrine and paracrine mechanisms at long term. In Brattleboro rats, CsA induced activation of NCC, but not NKCC2, and parallel effects were obtained in cultured cells in the absence of AVP. Stimulation of cultured thick ascending limb cells with AVP agonist restored their responsiveness to CsA. Our results suggest that the direct epithelial action of calcineurin inhibition is sufficient for the activation of NCC, whereas its effect on NKCC2 is more complex and requires concomitant stimulation by AVP.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.