Tacrolimus 4‐hour monitoring in liver transplant patients is non‐inferior to trough monitoring: The randomized controlled FK04 trial

BACKGROUND: After liver transplantation (LT), tacrolimus and ciclosporin treatment can lead to, partially concentration‐dependent, chronic kidney disease. Monitoring ciclosporin with two‐hour levels reduced overexposure and led to better renal function than trough‐monitoring (C0). For tacrolimus, a 4‐hour level (C4) can give a reasonable approximation of total drug exposure. We evaluated whether monitoring tacrolimus in stable patients after LT by C4 was superior to C0 regarding renal function, rejection and metabolic parameters. METHODS: This open label randomized controlled trial compared C4 monitoring of tacrolimus BID (Prograft) to trough (C0) monitoring in stable LT recipients. The target range for C4 of 7.8–16 ng/ml was calculated to be comparable with target C0 of 4–8 ng/ml. Primary endpoint was the effect on renal function and secondary endpoints were the occurrence of treated biopsy‐proven acute rejection, blood pressure and metabolic parameters, during 3 months of follow‐up. RESULTS: Fifty patients were randomized to C0 (n = 25) or C4 (n = 25) monitoring. There was no difference in renal function between the C0 and the C4 group (p = .98 and p = .13 for CG and MDRD at 3 months). Also, the amount of proteinuria was similar (p = .59). None of the patients suffered from graft loss or was treated for rejection. Metabolic parameters did not differ between the two groups. CONCLUSION: Tacrolimus 4‐hour monitoring in stable LT patients is not superior to trough monitoring, regarding the effect on renal function, but is safe for use to facilitate tacrolimus monitoring in an afternoon outpatient clinic.