Effect of low-dose tacrolimus with mycophenolate mofetil on renal function following liver transplantation

Abstract

Aim: To determine whether low-dose tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is a safe approach to decrease the incidence of chronic kidney disease (CKD) in liver transplantation (LT) recipients.

Methods: We analyzed the medical records of 689 patients who underwent LT between March 1999 and December 2012 in a single Chinese center. Immunosuppression was initiated with a calcineurin inhibitor (TAC or CSA) and prednisone with or without MMF. CKD is defined by the glomerular filtration rate (GFR), estimated by an abbreviated Modification of Diet in Renal Disease formula, < 60 mL/min per 1.73 m(2) for at least 3 consecutive months after LT. Individuals with TAC trough concentrations ≤ 8 ng/mL at 3 mo after LT were defined as the low-dose group. The incidence of CKD within 5 years was compared between the TAC group and the CSA group, as well as between four subgroups (low-dose and high-dose TAC groups with or without MMF).

Results: No difference regarding the occurrence of pre-LT renal dysfunction or that of post-LT rejection was found between the TAC and CSA groups or between the four subgroups. With a definition of GFR < 60 mL/min per 1.73 m(2), the overall incidence of CKD was significantly higher in the CSA group than in the TAC group. The incidence of CKD in the low-dose TAC + MMF group (7.7%) was significantly lower than that observed in the low-dose TAC group (15.9%), high-dose TAC group (24.6%) and high-dose TAC + MMF group (18.5%). The cumulative 1-, 3- and 5-year incidence rates of CKD were 12.7%, 14.5% and 16.7%, respectively. The cumulative 5-year survival rates were 61.7% and 82.2% in patients with or without CKD, respectively.

Conclusion: In LT patients, the choice of immunosuppressive therapy appears to affect renal function and patient survival.

Keywords: Calcineurin inhibitor; Chronic kidney disease; Liver transplantation; Mycophenolate mofetil.

Figure 1

Incidence of chronic kidney disease. A: Incidence of chronic kidney disease (CKD) in the tacrolimus (TAC) and cyclosporine A (CSA) groups (P < 0.05); B: Incidence of CKD in the four TAC subgroups (P < 0.05). The estimated glomerular filtration rate (eGFR) was calculated by the abbreviated modification of diet in renal disease formula after each patient visit. Once the criterion for CKD (eGFR < 60 mL/min per 1.73 m²) was met, the patient was registered in the CKD group.

Figure 2

Kaplan-Meier analysis of cumulative patient survival in patients with and without chronic kidney disease. The cumulative survival was significantly higher in the non-chronic kidney disease (CKD) group (log-rank test, P < 0.05).