CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

B. Krämer¹, G. Mondragon-ramirez², E. Cassuto-viguier^3
1Medizinische Klinik I, Marienhospital Herne, Herne/GERMANY, ², Instituto Mexicano de Transplantes, Cuernavaca/MEXICO, ³, Service de Nephrologie, Nice/FRANCE

Body: Introduction: Once-daily prolonged-release tacrolimus (Tacrolimus QD) has shown similar efficacy and safety to the established twice-daily tacrolimus formulation in kidney transplantation. The aim of this prospective follow-up study was to assess long-term efficacy, safety and effect on renal function of Tacrolimus QD. Methods: This was a multicenter, single-arm, open, prospective, additional 2-year follow-up study of Tacrolimus QD treatment in adult renal transplant recipients who had already participated in a Phase III study (12-03) and received Tacrolimus QD from transplantation for 12–26 months duration (mean time post-transplant approximately 18 months). Entry to this follow-up study was at the discretion of patient and investigator. Patients’ original immunosuppressive regimen was maintained unless medical needs necessitated otherwise. Primary endpoints were patient and graft survival; secondary endpoints included adverse events (AEs), BPAR incidence and renal function (Cockcroft–Gault). Biopsy was performed for suspected rejection. Results: Data are presented from the follow-up period only and do not include results from the original study. 191 of 341 eligible kidney transplant recipients were enrolled into the follow-up study. 163 (85.3%) patients completed the 2-year follow-up. 27 (14.1%) patients were withdrawn: due to an AE (9), withdrawal of consent (4), pregnancy (3), prohibited medication (3), switch to regimen not containing Tacrolimus QD (2), non-compliance (1), lost to follow-up (1), and ‘other’ (4). Tacrolimus dosing and whole-blood trough levels decreased slightly over the follow-up period (Table 1). Graft loss occurred in 5 (2.6%) patients; 1 due to death, 2 due to chronic allograft dysfunction, 1 due to acute rejection and 1 due to ureter stenosis. Graft and patient survival was 97.4% and 99.3% during this 2-year follow-up (Kaplan–Meier). The 1 death was due to myocardial infarction (unlikely to be related to study drug). 1 BPAR episode occurred, which was corticosteroid-sensitive and mild. Most commonly reported causally related AEs were hypertension (8.9 %), urinary tract infection (6.8%), tremor (6.3%) and non-insulin dependent diabetes mellitus (5.8%). Mean serum creatinine (±SD) was 131.6 (50.3) at Day 1 of follow-up, decreasing to 126.7 (42.2) µmol/L at the end of the follow-up. Mean creatinine clearance (±SD) was 66.1 (22.0) at Day 1 of follow-up, increasing to 70.0 (26.3) mL/min at the end of the follow-up. Conclusions: These results demonstrate that once-daily prolonged-release tacrolimus is efficacious and well tolerated in the long-term in de novo treated kidney transplant recipients without compromising renal function.

Disclosure: All authors have declared no conflicts of interest.