Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation

BACKGROUND: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7–11 weeks post-HTx or standard CNI immunosuppression. RESULTS: In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=−0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR (Δ1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. CONCLUSIONS: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression.