Renal Recovery After Conversion to an Everolimus-Based Immunosuppression in Early and Late Heart Transplant Recipients: A 12-Month Analysis

Abstract

Objectives: Calcineurin inhibitor-induced nephrotoxicity reduces long-term patient survival after heart transplant. Proliferation signal inhibitors, in combination with or replacing calcineurin inhibitors, may preserve or improve renal function. We evaluated the effect of calcineurin inhibitor-reduction and withdrawal in everolimus-based immunosuppression on renal function after a heart transplant. Materials and Methods: Twenty-four patients with creatinine clearance < 1 mL/s (60 mL/min) were switched from tacrolimus and mycophenolate mofetil to low-dose tacrolimus/everolimus if their heart transplant was ≤ 1 year ago (group 1, n=13) and to everolimus/mycophenolate mofetil if their heart transplant was > 1 year ago (group 2, n=11). Serum creatinine levels and calculated creatinine clearance were analyzed up to 12 months after conversion. Results: The switch in immunosuppression was associated with a significant decrease/increase of serum creatinine/creatinine clearance in both groups between baseline and month 12 (group 1, creatinine, 221.0 ± 70.7 to 159.1 ± 44.2 µmol/L (2.5 ± 0.8 to 1.8 ± 0.5 mg/dL); creatinine clearance, 0.75 ± 0.45 to 1.01 ± 0.50 mL/s (45.1 ± 26.7 to 60.5 ± 29.7 mL/min) (P < .01 each); group 2, creatinine, 247.5 ± 79.6 to 159.1 ± 44.2 µmol/L (2.8 ± 0.9 to 1.8 ± 0.5 mg/dL), creatinine clearance, 0.57 ± 0.23 to 0.93 ± 0.33 mL/s (34.1 ± 13.8 to 55.7 ± 19.6 mL/min) [P < .05 each]) with no significant group difference in the creatinine and the creatinine clearance levels after switching. No acute rejections or deaths occurred during the 12-month follow-up. Four patients (36.4%) from group 2 and 1 patient (7.7%) from group 1 discontinued everolimus because of adverse events. Conclusions: Everolimus allows calcineurin inhibitorreduction and withdrawal after heart transplantion resulting in improved renal function. However, adverse effects are common and lead to a high reconversion rate.

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial

“…It is feasible that adjunctive therapy with MPA as well as low‐exposure CNI in the everolimus‐treated group may have contributed to the development of pneumonia and other infections. One small retrospective study has shown that starting everolimus with reduced‐exposure CNI but without MPA can maintain immunosuppressive efficacy , an approach which merits further investigation. No other notable safety differences were observed between groups, including the incidence and type of major adverse cardiac events, although there was a nonsignificant trend to higher triglyceride levels in the everolimus cohort.…”

Conversion to everolimus in pediatric heart transplant recipients is a safe treatment option with an impact on cardiac allograft vasculopathy and renal function

“…In our study, the evaluation of the development of the CrCl of all patients showed a significant improvement six, 12, and 24 months after conversion in comparison with the baseline. Previous studies have already indicated a positive renal effect (improvement or maintenance of renal function) of EVL use in combination with a reduced CNI dose 11‐13,21 . The NOCET study showed an improvement in renal function after conversion to EVL compared with standard CNI therapy after 12 and 24 months in patients older than 18 years of age at HTX 22 .…”