Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat model

Takeshi F. Andoh, Emmanuel A. Burdmann, Jessie Lindsley, Donald Houghton, William M. Bennett

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

FK506 can show efficacy in transplant rejection even after other immunosuppressive drugs have been ineffective. However, the lack of a suitable animal model has hindered the study of FK nephrotoxicity, which has been noted as a common adverse effect in human trials. In this paper, we report a model of chronic FK nephrotoxicity in which renal structure and function are worsened by sodium depletion. Pairfed male Sprague-Dawley rats were given FK (6 mg/kg p.o.) or vehicle for 21 days on a low-salt or normal diet. There was no significant difference in body weight between FK and vehicle groups. The FK whole-blood trough levels (3–10 ng/ml) in rats are similar to those in FK treated transplant patients. In sodium-depleted rats, FK clearly decreased GFR (0.09±0.03 ml/min/100 g vs. 0.94±0.06 ml/min/100 g in the vehicle group, P

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalTransplantation
Volume57
Issue number4
StatePublished - 1994

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Tacrolimus
Theoretical Models
Sodium
Graft Rejection
Immunosuppressive Agents
Sprague Dawley Rats
Animal Models
Salts
Body Weight
Diet
Transplants
Kidney
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Andoh, T. F., Burdmann, E. A., Lindsley, J., Houghton, D., & Bennett, W. M. (1994). Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat model. Transplantation, 57(4), 483-489.

Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat model. / Andoh, Takeshi F.; Burdmann, Emmanuel A.; Lindsley, Jessie; Houghton, Donald; Bennett, William M.

In: Transplantation, Vol. 57, No. 4, 1994, p. 483-489.

Research output: Contribution to journalArticle

Andoh, TF, Burdmann, EA, Lindsley, J, Houghton, D & Bennett, WM 1994, 'Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat model', Transplantation, vol. 57, no. 4, pp. 483-489.
Andoh, Takeshi F. ; Burdmann, Emmanuel A. ; Lindsley, Jessie ; Houghton, Donald ; Bennett, William M. / Enhancement of FK506 nephrotoxicity by sodium depletion in an experimental rat model. In: Transplantation. 1994 ; Vol. 57, No. 4. pp. 483-489.
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