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Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine
Author(s) -
Shihab Fuad S.,
Cibrik Diane,
Chan Laurence,
Kim Yu Seun,
Carmellini Mario,
Walker Rowan,
Zibari Gazi,
Pattison James,
CornuArtis Catherine,
Wang Zailong,
TedescoSilva Jr Helio
Publication year - 2012
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12045
Subject(s) - everolimus , medicine , urology , proteinuria , renal function , calcineurin , trough level , kidney disease , sirolimus , creatinine , gastroenterology , diabetes mellitus , transplantation , kidney , tacrolimus , endocrinology
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 ( C s A ) 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 C s A <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 C s A .