Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients

Jeffrey J. Gaynor, Gaetano Ciancio, Giselle Guerra, Junichiro Sageshima, David Roth, Linda Chen, Warren Kupin, Adela Mattiazzi, Lissett Tueros, Sandra Flores, Lois Hanson, Rodrigo Vianna, George W. Burke

Research output: Contribution to journalArticle

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Abstract

Background: A multivariable linear regression model including baseline and immunosuppression-related predictors of the post-kidney transplant tacrolimus dose/day required for achieving a target tacrolimus trough level of 4-8 ng/mL (currently accepted reduced tacrolimus dosing strategy) would provide a practical guide to clinicians. Methods: Using our prospectively followed cohort of 578 adult primary kidney transplant recipients assigned to receive reduced tacrolimus dosing as part of maintenance therapy, we determined the significant predictors of absolute tacrolimus dose (mg), tacrolimus trough level (ng/mL), and dose-adjusted tacrolimus trough level (%/L) during the first 36 months post-transplant. Results: Two demographic variables were associated with a significantly higher tacrolimus dose at each post-transplant time analyzed: African American recipient (p < 0.000001) and younger recipient age (p ≤ 0.00009). Use of maintenance corticosteroids was also associated with a significantly higher tacrolimus dose but only during the first 12 months post-transplant (p ≤ 0.002). None of the other baseline variables (or use of sirolimus) were predictive of tacrolimus dose, and none of these factors were associated with the tacrolimus trough level (thus, effective therapeutic drug monitoring was achieved). Results for dose-adjusted tacrolimus trough level were inversely related to the tacrolimus dose findings. Conclusions: Significantly higher tacrolimus dosing to achieve the target tacrolimus trough level (lower bioavailability) was required, but only among African Americans, younger recipients, and those receiving maintenance corticosteroids.

Original languageEnglish (US)
Pages (from-to)470-478
Number of pages9
JournalClinical Transplantation
Volume28
Issue number4
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Tacrolimus
Transplants
Kidney
Transplant Recipients
African Americans
Linear Models
Adrenal Cortex Hormones
Maintenance
Drug Monitoring
Sirolimus
Immunosuppression
Biological Availability

Keywords

  • Dose
  • Dose-adjusted trough level
  • Kidney transplantation
  • Tacrolimus
  • Trough level

ASJC Scopus subject areas

  • Transplantation

Cite this

Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients. / Gaynor, Jeffrey J.; Ciancio, Gaetano; Guerra, Giselle; Sageshima, Junichiro; Roth, David; Chen, Linda; Kupin, Warren; Mattiazzi, Adela; Tueros, Lissett; Flores, Sandra; Hanson, Lois; Vianna, Rodrigo; Burke, George W.

In: Clinical Transplantation, Vol. 28, No. 4, 01.01.2014, p. 470-478.

Research output: Contribution to journalArticle

Gaynor, JJ, Ciancio, G, Guerra, G, Sageshima, J, Roth, D, Chen, L, Kupin, W, Mattiazzi, A, Tueros, L, Flores, S, Hanson, L, Vianna, R & Burke, GW 2014, 'Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients', Clinical Transplantation, vol. 28, no. 4, pp. 470-478. https://doi.org/10.1111/ctr.12340
Gaynor, Jeffrey J. ; Ciancio, Gaetano ; Guerra, Giselle ; Sageshima, Junichiro ; Roth, David ; Chen, Linda ; Kupin, Warren ; Mattiazzi, Adela ; Tueros, Lissett ; Flores, Sandra ; Hanson, Lois ; Vianna, Rodrigo ; Burke, George W. / Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients. In: Clinical Transplantation. 2014 ; Vol. 28, No. 4. pp. 470-478.
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T1 - Predictors of reduced tacrolimus dose and trough level through 36 months post-transplant among 578 adult primary kidney transplant recipients

AU - Gaynor, Jeffrey J.

AU - Ciancio, Gaetano

AU - Guerra, Giselle

AU - Sageshima, Junichiro

AU - Roth, David

AU - Chen, Linda

AU - Kupin, Warren

AU - Mattiazzi, Adela

AU - Tueros, Lissett

AU - Flores, Sandra

AU - Hanson, Lois

AU - Vianna, Rodrigo

AU - Burke, George W.

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N2 - Background: A multivariable linear regression model including baseline and immunosuppression-related predictors of the post-kidney transplant tacrolimus dose/day required for achieving a target tacrolimus trough level of 4-8 ng/mL (currently accepted reduced tacrolimus dosing strategy) would provide a practical guide to clinicians. Methods: Using our prospectively followed cohort of 578 adult primary kidney transplant recipients assigned to receive reduced tacrolimus dosing as part of maintenance therapy, we determined the significant predictors of absolute tacrolimus dose (mg), tacrolimus trough level (ng/mL), and dose-adjusted tacrolimus trough level (%/L) during the first 36 months post-transplant. Results: Two demographic variables were associated with a significantly higher tacrolimus dose at each post-transplant time analyzed: African American recipient (p < 0.000001) and younger recipient age (p ≤ 0.00009). Use of maintenance corticosteroids was also associated with a significantly higher tacrolimus dose but only during the first 12 months post-transplant (p ≤ 0.002). None of the other baseline variables (or use of sirolimus) were predictive of tacrolimus dose, and none of these factors were associated with the tacrolimus trough level (thus, effective therapeutic drug monitoring was achieved). Results for dose-adjusted tacrolimus trough level were inversely related to the tacrolimus dose findings. Conclusions: Significantly higher tacrolimus dosing to achieve the target tacrolimus trough level (lower bioavailability) was required, but only among African Americans, younger recipients, and those receiving maintenance corticosteroids.

AB - Background: A multivariable linear regression model including baseline and immunosuppression-related predictors of the post-kidney transplant tacrolimus dose/day required for achieving a target tacrolimus trough level of 4-8 ng/mL (currently accepted reduced tacrolimus dosing strategy) would provide a practical guide to clinicians. Methods: Using our prospectively followed cohort of 578 adult primary kidney transplant recipients assigned to receive reduced tacrolimus dosing as part of maintenance therapy, we determined the significant predictors of absolute tacrolimus dose (mg), tacrolimus trough level (ng/mL), and dose-adjusted tacrolimus trough level (%/L) during the first 36 months post-transplant. Results: Two demographic variables were associated with a significantly higher tacrolimus dose at each post-transplant time analyzed: African American recipient (p < 0.000001) and younger recipient age (p ≤ 0.00009). Use of maintenance corticosteroids was also associated with a significantly higher tacrolimus dose but only during the first 12 months post-transplant (p ≤ 0.002). None of the other baseline variables (or use of sirolimus) were predictive of tacrolimus dose, and none of these factors were associated with the tacrolimus trough level (thus, effective therapeutic drug monitoring was achieved). Results for dose-adjusted tacrolimus trough level were inversely related to the tacrolimus dose findings. Conclusions: Significantly higher tacrolimus dosing to achieve the target tacrolimus trough level (lower bioavailability) was required, but only among African Americans, younger recipients, and those receiving maintenance corticosteroids.

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KW - Dose-adjusted trough level

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KW - Tacrolimus

KW - Trough level

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