Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine

Fuad S. Shihab, Diane Cibrik, Laurence Chan, Yu Seun Kim, Mario Carmellini, Rowan Walker, Gazi Zibari, James Pattison, Catherine Cornu-Artis, Zailong Wang, Helio Tedesco-Silva

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations. Results: The incidence of treated biopsy-proven acute rejection and graft loss at month 12 was highest in patients with everolimus <3 ng/mL (36.4% and 28.6%, respectively, vs. 9.1-15.3% and 0.9-5.0% with higher concentration ranges). A higher mortality rate was observed in patients with an everolimus trough concentration ≥12 ng/mL (10.0% vs. 1.7-5.6% with lower concentration ranges). The lowest rates of renal dysfunction (defined as poor renal function [estimated GFR, serum creatinine] or proteinuria), wound healing events, peripheral edema, new-onset diabetes mellitus, hypercholesterolemia and hypertriglyceridemia were generally observed with everolimus trough concentration in the range 3-8 ng/mL and CsA <100 ng/mL. Proteinuria occurred most frequently in patients with very low or very high everolimus trough concentrations. Conclusions: These results support an exposure-response relationship between clinical events and everolimus trough concentrations in kidney transplant patients receiving reduced-exposure CsA.

Original languageEnglish
Pages (from-to)217-226
Number of pages10
JournalClinical Transplantation
Volume27
Issue number2
DOIs
Publication statusPublished - 2013 Mar 1

Fingerprint

Cyclosporine
Transplants
Kidney
Proteinuria
Everolimus
Hypertriglyceridemia
Graft Rejection
Hypercholesterolemia
Wound Healing
Edema
Creatinine
Diabetes Mellitus
Randomized Controlled Trials
Steroids
Biopsy
Mortality
Incidence
Serum

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Shihab, Fuad S. ; Cibrik, Diane ; Chan, Laurence ; Kim, Yu Seun ; Carmellini, Mario ; Walker, Rowan ; Zibari, Gazi ; Pattison, James ; Cornu-Artis, Catherine ; Wang, Zailong ; Tedesco-Silva, Helio. / Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine. In: Clinical Transplantation. 2013 ; Vol. 27, No. 2. pp. 217-226.
@article{66aa036791e64975bae468a153fe7b9a,
title = "Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine",
abstract = "Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations. Results: The incidence of treated biopsy-proven acute rejection and graft loss at month 12 was highest in patients with everolimus <3 ng/mL (36.4{\%} and 28.6{\%}, respectively, vs. 9.1-15.3{\%} and 0.9-5.0{\%} with higher concentration ranges). A higher mortality rate was observed in patients with an everolimus trough concentration ≥12 ng/mL (10.0{\%} vs. 1.7-5.6{\%} with lower concentration ranges). The lowest rates of renal dysfunction (defined as poor renal function [estimated GFR, serum creatinine] or proteinuria), wound healing events, peripheral edema, new-onset diabetes mellitus, hypercholesterolemia and hypertriglyceridemia were generally observed with everolimus trough concentration in the range 3-8 ng/mL and CsA <100 ng/mL. Proteinuria occurred most frequently in patients with very low or very high everolimus trough concentrations. Conclusions: These results support an exposure-response relationship between clinical events and everolimus trough concentrations in kidney transplant patients receiving reduced-exposure CsA.",
author = "Shihab, {Fuad S.} and Diane Cibrik and Laurence Chan and Kim, {Yu Seun} and Mario Carmellini and Rowan Walker and Gazi Zibari and James Pattison and Catherine Cornu-Artis and Zailong Wang and Helio Tedesco-Silva",
year = "2013",
month = "3",
day = "1",
doi = "10.1111/ctr.12045",
language = "English",
volume = "27",
pages = "217--226",
journal = "Clinical Transplantation",
issn = "0902-0063",
publisher = "Wiley-Blackwell",
number = "2",

}

Shihab, FS, Cibrik, D, Chan, L, Kim, YS, Carmellini, M, Walker, R, Zibari, G, Pattison, J, Cornu-Artis, C, Wang, Z & Tedesco-Silva, H 2013, 'Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine', Clinical Transplantation, vol. 27, no. 2, pp. 217-226. https://doi.org/10.1111/ctr.12045

Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine. / Shihab, Fuad S.; Cibrik, Diane; Chan, Laurence; Kim, Yu Seun; Carmellini, Mario; Walker, Rowan; Zibari, Gazi; Pattison, James; Cornu-Artis, Catherine; Wang, Zailong; Tedesco-Silva, Helio.

In: Clinical Transplantation, Vol. 27, No. 2, 01.03.2013, p. 217-226.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine

AU - Shihab, Fuad S.

AU - Cibrik, Diane

AU - Chan, Laurence

AU - Kim, Yu Seun

AU - Carmellini, Mario

AU - Walker, Rowan

AU - Zibari, Gazi

AU - Pattison, James

AU - Cornu-Artis, Catherine

AU - Wang, Zailong

AU - Tedesco-Silva, Helio

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations. Results: The incidence of treated biopsy-proven acute rejection and graft loss at month 12 was highest in patients with everolimus <3 ng/mL (36.4% and 28.6%, respectively, vs. 9.1-15.3% and 0.9-5.0% with higher concentration ranges). A higher mortality rate was observed in patients with an everolimus trough concentration ≥12 ng/mL (10.0% vs. 1.7-5.6% with lower concentration ranges). The lowest rates of renal dysfunction (defined as poor renal function [estimated GFR, serum creatinine] or proteinuria), wound healing events, peripheral edema, new-onset diabetes mellitus, hypercholesterolemia and hypertriglyceridemia were generally observed with everolimus trough concentration in the range 3-8 ng/mL and CsA <100 ng/mL. Proteinuria occurred most frequently in patients with very low or very high everolimus trough concentrations. Conclusions: These results support an exposure-response relationship between clinical events and everolimus trough concentrations in kidney transplant patients receiving reduced-exposure CsA.

AB - Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored. Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations. Results: The incidence of treated biopsy-proven acute rejection and graft loss at month 12 was highest in patients with everolimus <3 ng/mL (36.4% and 28.6%, respectively, vs. 9.1-15.3% and 0.9-5.0% with higher concentration ranges). A higher mortality rate was observed in patients with an everolimus trough concentration ≥12 ng/mL (10.0% vs. 1.7-5.6% with lower concentration ranges). The lowest rates of renal dysfunction (defined as poor renal function [estimated GFR, serum creatinine] or proteinuria), wound healing events, peripheral edema, new-onset diabetes mellitus, hypercholesterolemia and hypertriglyceridemia were generally observed with everolimus trough concentration in the range 3-8 ng/mL and CsA <100 ng/mL. Proteinuria occurred most frequently in patients with very low or very high everolimus trough concentrations. Conclusions: These results support an exposure-response relationship between clinical events and everolimus trough concentrations in kidney transplant patients receiving reduced-exposure CsA.

UR - http://www.scopus.com/inward/record.url?scp=84876093222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876093222&partnerID=8YFLogxK

U2 - 10.1111/ctr.12045

DO - 10.1111/ctr.12045

M3 - Article

C2 - 23230975

AN - SCOPUS:84876093222

VL - 27

SP - 217

EP - 226

JO - Clinical Transplantation

JF - Clinical Transplantation

SN - 0902-0063

IS - 2

ER -