Nephrotoxicity of immunosuppressive drugs: New insight and preventive strategies

A. J. Olyaei, Angelo M DeMattos, W. M. Bennett

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Cyclosporine and tacrolimus reduce allograft rejection, improve allograft half-life and patient survival. Ironically, the nephrotoxicity of these agents may adversely affect allograft survival in renal transplant recipients or cause end-stage renal diseases in other solid organ and bone marrow transplant recipients. Acute dose-dependent and chronic non-dose-dependent nephrotoxicity has been reported in both transplant recipients and patients with autoimmune disorders. Preliminary evidence suggests that drug therapeutic monitoring has little value in the diagnosis or management of nephrotoxicity associated with calcineurin inhibitors. Although the exact mechanism of nephrotoxicity is not fully understood, several factors have been implicated in the pathogenesis of immunosuppressive-induced nephrotoxicity. Renal and systemic vasoconstriction, increased release of endothelin-1, decreased production of nitric acid and increased expression of TGF-beta are the major adverse pathophysiologic abnormalities of these agents. Reducing the dose of a calcineurin inhibitor, or using protocols without calcineurin inhibition may ultimately minimize the risk of drug toxicity and improve allograft and patient survival. New experiences with non-nephrotoxic agents and protocols including mycophenolate and sirolimus allow for early calcineurin inhibitor reduction or elimination without increasing the risk of allograft rejection.

Original languageEnglish (US)
Pages (from-to)384-389
Number of pages6
JournalCurrent Opinion in Critical Care
Volume7
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Immunosuppressive Agents
Allografts
Pharmaceutical Preparations
Kidney
Nitric Acid
Survival
Drug Monitoring
Calcineurin
Tacrolimus
Endothelin-1
Sirolimus
Vasoconstriction
Drug-Related Side Effects and Adverse Reactions
Transforming Growth Factor beta
Cyclosporine
Chronic Kidney Failure
Half-Life
Bone Marrow
Transplant Recipients
Calcineurin Inhibitors

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Nephrotoxicity of immunosuppressive drugs : New insight and preventive strategies. / Olyaei, A. J.; DeMattos, Angelo M; Bennett, W. M.

In: Current Opinion in Critical Care, Vol. 7, No. 6, 2001, p. 384-389.

Research output: Contribution to journalArticle

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