TY - JOUR
T1 - Nephrotoxicity of immunosuppressive drugs
T2 - New insight and preventive strategies
AU - Olyaei, A. J.
AU - De Mattos, A. M.
AU - Bennett, W. M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1097/00075198-200112000-00003
DO - 10.1097/00075198-200112000-00003
M3 - Review article
C2 - 11805539
AN - SCOPUS:0035659395
SN - 1070-5295
VL - 7
SP - 384
EP - 389
JO - Current Opinion in Critical Care
JF - Current Opinion in Critical Care
IS - 6
ER -