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.
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 language | English |
|---|---|
| Pages (from-to) | 217-226 |
| Number of pages | 10 |
| Journal | Clinical Transplantation |
| Volume | 27 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2013 |
Keywords
- efficacy
- everolimus
- exposure
- kidney transplantation
- therapeutic drug monitoring
- GLOMERULAR-FILTRATION-RATE
- RENAL-TRANSPLANTATION
- SDZ RAD
- MULTICENTER
- TACROLIMUS
- RECIPIENTS
- EFFICACY
- SAFETY
- TRIAL
