Background: Tacrolimus (FK506) is an effective part of drug protocols for immunosuppression after
heart transplantation (HTx). However, tacrolimus is associated with long-term kidney
function decline and adverse events in patients undergoing HTx. We hypothesize that
extended-release tacrolimus given once daily (Advagraf, ADV) is associated with lower
decline in kidney function due to its pharmacokinetics with once-daily peak levels
and the higher adherence to therapy with administration once-daily compared with twice-daily
tacrolimus (Prograf, PRO).
Methods: We retrospectively analyzed the decline in estimated glomerular filtration rate (eGFR)
in all cases of HTx at our center. Patients with combined heart and kidney transplant,
with CKD V requiring hemodialysis, and with missing longitudinal laboratory values
were excluded. We compared the decline of eGFR between the first follow-up after HTx,
the time of switching from PRO to ADV, and the last follow-up at our center. To avoid
false low eGFR values due to acute kidney injury, we used the best eGFR in a time
span of 14 days around these dates. We also assessed demographic values, comorbidities,
other drugs of immunosuppressive protocol, and mean FK506 levels.
Results: A total number of 175 patients was analyzed. At analysis, 105 patients received PRO
and 70 patients ADV. The mean age was 54 years with 22% females. Baseline eGFR was
62 mL/min. The decrease in eGFR per patient-year at ADV was lower compared with patient-year
at PRO (−0.5 ± 15 mL/min/year versus −10.3 ± 36.9 mL/min/year; p = 0.043). This was represented in a trend for lower eGFR decrease in patients receiving
either ADV from the beginning or being switched from PRO to ADV compared with patients
receiving PRO (−0.5 ± 15 mL/min/year on ADV versus −6.5 ± 23.4 mL/min/year on PRO;
p = 0.075). In multivariate analysis including age, second immunosuppressive agent
(mycophenolate mofetil or everolimus), and mean FK506 levels, only ADV was associated
with lower decrease in eGFR (p = 0.032).
Conclusion: ADV is associated with less decrease in eGFR after HTx compared with PRO. Early switch
to ADV could possibly prevent decrease in kidney function and adverse events. The
findings presented here describe real-world experience with the inherent limitations
of observational studies in establishing causal relationships and might be confounded
due to variable eGFR values in early recovery time after HTx and individual decision
for timing of switching from PRO to ADV.
