Background: Renal impairment and high model of end-stage liver disease scores before liver transplantation (LT) are increasingly common.
Patients and methods: This was a single-arm, 2-step prospective trial of bottom-up calcineurin inhibitor (CNI)-free de novo immunosuppressive treatment (mycofenolate mofetil, steroids, basiliximab) with delayed introduction of sirolimus in patients with renal impairment. Primary endpoint was immunologic safety assessed by the incidence of steroid-resistant rejection within the first 30 days after liver transplantation.
Results: Twenty-seven patients were included with a median age of 56 years and labMELD of 28. Baseline glomerular filtration rate was 38 (Cockroft-Gault) and 24 mL/min (modification of diet in renal disease). No steroid-resistant rejections occurred within 30 days. Incidence of biopsy proven acute rejection was 18.5%. Sirolimus was started on day 10 (range, day 1 to day 48). The rate switched to CNI treatment by 1 year was 44%; 1-year overall survival was 93%. Renal function improved significantly, reflected by a Δglomerular filtration rate of 31 mL/min from baseline to 1 year (P = 0.006). Per protocol analysis revealed freedom from CNI, but not presence of sirolimus within the first 30 days, as critical for renal recovery.
Conclusions: Initial de novo CNI-free immunosuppressive bottom-up treatment is safe in selected patient groups. The critical period for relevant recovery of renal function seems to be the early period (first 30 days), independent from presence of sirolimus.
Trial registration: ClinicalTrials.gov NCT00604357.