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.

• Authors: 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 Jr
• Journal: Clinical transplantation (Clin Transplant) 2013 Mar-Apr Vol. 27 Issue 2 Pg. 217-26 ISSN: 1399-0012 [Electronic] Denmark
• PMID: 23230975 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Immunosuppressive Agents
• Cyclosporine
• Everolimus
• Sirolimus

Topics

• Adult
• Cyclosporine (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Monitoring
• Drug Therapy, Combination
• Everolimus
• Female
• Follow-Up Studies
• Graft Rejection (epidemiology, prevention & control)
• Graft Survival
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Kidney Transplantation
• Linear Models
• Logistic Models
• Male
• Middle Aged
• Postoperative Complications (chemically induced, epidemiology, prevention & control)
• Sirolimus (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Survival Analysis
• Treatment Outcome