Pathogenesis of calcineurin inhibitor-induced hypertension

Ewout J. Hoorn, Stephen B. Walsh, James (Jim) McCormick, Robert Zietse, Robert J. Unwin, David Ellison

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

This article reviews the current understanding of the mechanisms of calcineurin inhibitor-induced hypertension. Already early after the introduction of cyclosporine in the 1980s, vasoconstriction, sympathetic excitation and sodium retention by the kidney had been shown to play a role in this form of hypertension. The vasoconstrictive effects of calcineurin inhibitors are related to interference with the balance of vasoactive substances, including endothelin and nitric oxide. Until recently, the renal site of the sodium-retaining effect of calcineurin inhibitors was unknown. We and others have shown that calcineurin inhibitors increase the activity of the thiazide-sensitive sodium chloride cotransporter through an effect on the kinases WNK and SPAK. Here, we review the pertinent literature on the hypertensinogenic effects of calcineurin inhibitors, including neural, vascular and renal effects, and we propose an integrated model of calcineurin inhibitor- induced hypertension.

Original languageEnglish (US)
Pages (from-to)269-275
Number of pages7
JournalJournal of Nephrology
Volume25
Issue number3
DOIs
StatePublished - Jun 2012

Fingerprint

Hypertension
Kidney
Member 3 Solute Carrier Family 12
Sodium
Endothelins
Vasoconstriction
Cyclosporine
Blood Vessels
Calcineurin Inhibitors
Nitric Oxide
Phosphotransferases

Keywords

  • Cyclosporine
  • Sodium chloride cotransporter
  • Tacrolimus
  • Vasoconstriction
  • WNK kinase

ASJC Scopus subject areas

  • Nephrology

Cite this

Pathogenesis of calcineurin inhibitor-induced hypertension. / Hoorn, Ewout J.; Walsh, Stephen B.; McCormick, James (Jim); Zietse, Robert; Unwin, Robert J.; Ellison, David.

In: Journal of Nephrology, Vol. 25, No. 3, 06.2012, p. 269-275.

Research output: Contribution to journalArticle

Hoorn, Ewout J. ; Walsh, Stephen B. ; McCormick, James (Jim) ; Zietse, Robert ; Unwin, Robert J. ; Ellison, David. / Pathogenesis of calcineurin inhibitor-induced hypertension. In: Journal of Nephrology. 2012 ; Vol. 25, No. 3. pp. 269-275.
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