Pathophysiological mechanisms of calcineurin inhibitor-induced nephrotoxicity and arterial hypertension

Title:

Pathophysiological mechanisms of calcineurin inhibitor-induced nephrotoxicity and arterial hypertension

Creator:

Lenka Hošková, Ivan Málek, Libor Kopkan, and Josef Kautzner

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:671a2338-c580-4d33-b7c3-425fc59e9020
uuid:671a2338-c580-4d33-b7c3-425fc59e9020
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, transplantace srdce, imunosuprese, nefrotoxicita, hypertenze, heart transplantation, immunosuppression, nephrotoxicity, hypertension, calcineurin inhibitor, pathophysiological mechanism, 14, and 612

Type:

article, články, journal articles, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Solid organ transplantation is an established treatment modality in patients with end-stage organ damage in cases where other therapeutic options fail. The long-term outcomes of solid organ transplant recipients have improved considerably since the introduction of the first calcineurin inhibitor (CNI) - cyclosporine. In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered. The immunosuppressive effects of CNIs result from the inhibition of interleukin-2 synthesis and reduced proliferation of T cells due to calcineurin blockade. The considerable side effects that are associated with CNIs therapy include arterial hypertension and nephrotoxicity. The focus of this article was to review the available literature on the pathophysiological mechanisms of CNIs that induce chronic nephrotoxicity and arterial hypertension. CNIs lead to activation of the major vasoconstriction systems, such as the reninangiotensin and endothelin systems, and increase sympathetic nerve activity. On the other hand, CNIs are known to inhibit NO synthesis and NO-mediated vasodilation and to increase free radical formation. Altogether, these processes cause endothelial dysfunction and contribute to the impairment of organ function. A better insight into the mechanisms underlying CNI nephrotoxicity could assist in developing more targeted therapies of arterial hypertension or preventing CNI nephrotoxicity in organ transplant recipients, including heart transplantation., L. Hošková, I. Málek, L. Kopkan, J. Kautzner., and Obsahuje bibliografii

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Source:

Physiological research | 2017 Volume:66 | Number:2

Harvested from:

CDK

Metadata only:

false