Nephrotoxicity of immunosuppressive drugs: Long-term consequences and challenges for the future

Angelo M DeMattos, Ali J. Olyaei, William M. Bennett

Research output: Contribution to journalArticle

334 Citations (Scopus)

Abstract

The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are associated with dose- and efficacy-limiting adverse events, including nephrotoxicity, which may diminish their overall benefits for long-term graft survival. Nephrotoxicity is difficult to distinguish from chronic allograft rejection and is a particular problem in the setting of renal transplantation. Minimizing immunosuppressant-induced nephrotoxicity could improve long-term renal allograft survival. However, to obtain significant long-term improvement in renal allograft outcomes, it may be necessary to adopt new immunosuppressive regimens that rely less on calcineurin inhibitors. Recipients of other transplanted organs, as well as patients with autoimmune diseases who require immunosuppressant therapy, could also benefit from this change in immunosuppressive drug strategy because their healthy, native kidneys are particularly susceptible to the nephrotoxic effects of CsA and FK506. CsA- and FK506-sparing regimens, which use reduced doses of CsA and FK506 in combination with other nonnephrotoxic immunosuppressants, may be the best current option for reducing nephrotoxicity. The chemical immunosuppressant mycophenolate mofetil (MMF) has been used as part of CsA- and FK506-sparing regimens that provide improved renal function while maintaining adequate immunosuppression. Such regimens should reduce patient morbidity and mortality. Also, because immunosuppressant-induced nephrotoxicity has been associated with significant financial costs, CsA- and FK506-sparing regimens should result in substantial savings in health care costs. (C) 2000 National Kidney Foundation, Inc.

Original languageEnglish (US)
Pages (from-to)333-346
Number of pages14
JournalAmerican Journal of Kidney Diseases
Volume35
Issue number2
StatePublished - 2000
Externally publishedYes

Fingerprint

Tacrolimus
Immunosuppressive Agents
Cyclosporine
Pharmaceutical Preparations
Allografts
Kidney
Mycophenolic Acid
Graft Survival
Health Care Costs
Kidney Transplantation
Immunosuppression
Autoimmune Diseases
Morbidity
Costs and Cost Analysis
Mortality

Keywords

  • Cyclosporine
  • Graft rejection
  • Immunosuppression
  • Mycophenolate mofetil
  • Nephrotoxicity
  • Renal function
  • Tacrolimus

ASJC Scopus subject areas

  • Nephrology

Cite this

Nephrotoxicity of immunosuppressive drugs : Long-term consequences and challenges for the future. / DeMattos, Angelo M; Olyaei, Ali J.; Bennett, William M.

In: American Journal of Kidney Diseases, Vol. 35, No. 2, 2000, p. 333-346.

Research output: Contribution to journalArticle

@article{f94919eb54974f20bb56da7462c3dad6,
title = "Nephrotoxicity of immunosuppressive drugs: Long-term consequences and challenges for the future",
abstract = "The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are associated with dose- and efficacy-limiting adverse events, including nephrotoxicity, which may diminish their overall benefits for long-term graft survival. Nephrotoxicity is difficult to distinguish from chronic allograft rejection and is a particular problem in the setting of renal transplantation. Minimizing immunosuppressant-induced nephrotoxicity could improve long-term renal allograft survival. However, to obtain significant long-term improvement in renal allograft outcomes, it may be necessary to adopt new immunosuppressive regimens that rely less on calcineurin inhibitors. Recipients of other transplanted organs, as well as patients with autoimmune diseases who require immunosuppressant therapy, could also benefit from this change in immunosuppressive drug strategy because their healthy, native kidneys are particularly susceptible to the nephrotoxic effects of CsA and FK506. CsA- and FK506-sparing regimens, which use reduced doses of CsA and FK506 in combination with other nonnephrotoxic immunosuppressants, may be the best current option for reducing nephrotoxicity. The chemical immunosuppressant mycophenolate mofetil (MMF) has been used as part of CsA- and FK506-sparing regimens that provide improved renal function while maintaining adequate immunosuppression. Such regimens should reduce patient morbidity and mortality. Also, because immunosuppressant-induced nephrotoxicity has been associated with significant financial costs, CsA- and FK506-sparing regimens should result in substantial savings in health care costs. (C) 2000 National Kidney Foundation, Inc.",
keywords = "Cyclosporine, Graft rejection, Immunosuppression, Mycophenolate mofetil, Nephrotoxicity, Renal function, Tacrolimus",
author = "DeMattos, {Angelo M} and Olyaei, {Ali J.} and Bennett, {William M.}",
year = "2000",
language = "English (US)",
volume = "35",
pages = "333--346",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "2",

}

TY - JOUR

T1 - Nephrotoxicity of immunosuppressive drugs

T2 - Long-term consequences and challenges for the future

AU - DeMattos, Angelo M

AU - Olyaei, Ali J.

AU - Bennett, William M.

PY - 2000

Y1 - 2000

N2 - The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are associated with dose- and efficacy-limiting adverse events, including nephrotoxicity, which may diminish their overall benefits for long-term graft survival. Nephrotoxicity is difficult to distinguish from chronic allograft rejection and is a particular problem in the setting of renal transplantation. Minimizing immunosuppressant-induced nephrotoxicity could improve long-term renal allograft survival. However, to obtain significant long-term improvement in renal allograft outcomes, it may be necessary to adopt new immunosuppressive regimens that rely less on calcineurin inhibitors. Recipients of other transplanted organs, as well as patients with autoimmune diseases who require immunosuppressant therapy, could also benefit from this change in immunosuppressive drug strategy because their healthy, native kidneys are particularly susceptible to the nephrotoxic effects of CsA and FK506. CsA- and FK506-sparing regimens, which use reduced doses of CsA and FK506 in combination with other nonnephrotoxic immunosuppressants, may be the best current option for reducing nephrotoxicity. The chemical immunosuppressant mycophenolate mofetil (MMF) has been used as part of CsA- and FK506-sparing regimens that provide improved renal function while maintaining adequate immunosuppression. Such regimens should reduce patient morbidity and mortality. Also, because immunosuppressant-induced nephrotoxicity has been associated with significant financial costs, CsA- and FK506-sparing regimens should result in substantial savings in health care costs. (C) 2000 National Kidney Foundation, Inc.

AB - The calcineurin inhibitors cyclosporin A (CsA) and tacrolimus (FK506) are associated with dose- and efficacy-limiting adverse events, including nephrotoxicity, which may diminish their overall benefits for long-term graft survival. Nephrotoxicity is difficult to distinguish from chronic allograft rejection and is a particular problem in the setting of renal transplantation. Minimizing immunosuppressant-induced nephrotoxicity could improve long-term renal allograft survival. However, to obtain significant long-term improvement in renal allograft outcomes, it may be necessary to adopt new immunosuppressive regimens that rely less on calcineurin inhibitors. Recipients of other transplanted organs, as well as patients with autoimmune diseases who require immunosuppressant therapy, could also benefit from this change in immunosuppressive drug strategy because their healthy, native kidneys are particularly susceptible to the nephrotoxic effects of CsA and FK506. CsA- and FK506-sparing regimens, which use reduced doses of CsA and FK506 in combination with other nonnephrotoxic immunosuppressants, may be the best current option for reducing nephrotoxicity. The chemical immunosuppressant mycophenolate mofetil (MMF) has been used as part of CsA- and FK506-sparing regimens that provide improved renal function while maintaining adequate immunosuppression. Such regimens should reduce patient morbidity and mortality. Also, because immunosuppressant-induced nephrotoxicity has been associated with significant financial costs, CsA- and FK506-sparing regimens should result in substantial savings in health care costs. (C) 2000 National Kidney Foundation, Inc.

KW - Cyclosporine

KW - Graft rejection

KW - Immunosuppression

KW - Mycophenolate mofetil

KW - Nephrotoxicity

KW - Renal function

KW - Tacrolimus

UR - http://www.scopus.com/inward/record.url?scp=0033979599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033979599&partnerID=8YFLogxK

M3 - Article

C2 - 10676738

AN - SCOPUS:0033979599

VL - 35

SP - 333

EP - 346

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

IS - 2

ER -