Prophylaxis of chronic kidney disease after liver transplantation--experience from west China

Abstract

Aim: To evaluate the prophylaxis of chronic kidney disease (CKD) after liver transplantation (LT) with low-dose calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF).

Methods: From March 1999 to December 2009, a total of 572 patients (478 males and 94 females) underwent LT enrolled in the study. Initial immunosuppression was by triple-drug regimens that included a CNI, MMF, and prednisone. The initial dose of CNI was 0.05-0.10 mg/kg per day for tacrolimus (TAC) and 5-10 mg/kg per d for cyclosporine A (CSA) respectively, and was gradually reduced based on a stable graft function. The serum trough level of CNI was 6-8 ng/mL for TAC and 120-150 ng/mL for CSA 3-mo post-operation, 4-6 ng/mL for TAC and 80-120 ng/mL for CSA 1-year after transplantation was expected with stable liver function. MMF was personalized between 1.0-1.5 g/d. Glomerular filtration rate (GFR) was estimated by an abbreviated Modification of Diet in Renal Disease formula. Risk factors of CKD were examined by univariate and multivariate logistic regression.

Results: With a definition of GFR < 60 mL/min per 1.73 m(2), the incidence of CKD was 17.3% 5-year after LT. There were 68.3% (293 of 429 cases) patients managed to control their TAC trough concentrations within 8 ng/mL and 58.0% (83 of 143 cases) patients' CSA trough concentrations within 150 ng/mL. Of the 450 recipients followed-up over 1 year, 55.5% (183 of 330 cases) of which were treated with TAC had a trough concentration ≤ 6 ng/mL while 65.8% (79 of 120 cases) of which were treated with CSA had a concentration ≤ 120 ng/mL. The incidence of CKD in the groups of lower CNI trough concentrations was significantly lower than the groups with CNI concentrations above the ideal range. Patients with CKD had much higher CNI trough concentrations than that of patients without CKD. MMF was adopted in 359 patients (62.8%). Patients administrated with MMF had a relatively low CNI trough concentrations but with no significant difference. The graft function remained stable during follow-up. No difference was found between different groups of CNI trough concentrations. Pre-LT renal dysfunction, ages, acute kidney injury, high blood trough concentrations of CNI in 3 mo (TAC > 8 ng/mL, CSA > 150 ng/mL) and hypertension after operation were associated with CKD progression, while male gender and adoption of MMF were protection factors.

Conclusion: Low dose of CNI combined with MMF managed to prevent CKD after LT with stable graft function.

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

Figure 1

Incidence of chronic kidney disease 5 years after liver transplantation. The estimated glomerular filtration rate (eGFR) was calculated by the abbreviated Modification of Diet in Renal Disease formula after each visit of a patient. And once met the criterion of chronic kidney disease (CKD) (eGFR < 60 mL/min per 1.73 m²), they were registered into the CKD group. Seventeen point three percents of the whole population (99 cases) developed CKD during the 5-year’s follow-up.

Figure 2

Calcineurin inhibitor trough concentrations between different groups. We compared the mean trough concentrations of tacrolimus (TAC) and cyclosporine A (CSA) at different time points between patients with and without chronic kidney disease (CKD) (A and B), between patients combined mycophenolate mofetil (MMF) use and no use (C and D). A: Trough concentrations of TAC grouped by CKD and non-CKD at different time points. Apart from 5 years after liver transplantation (LT), the CKD people had higher TAC trough concentrations than non-CKD people with statistical significance; B: Trough concentrations of CSA grouped by CKD and non-CKD at different time points. The CKD people had higher CSA trough concentrations than non-CKD people with statistical significance in 1, 2, 3, 4 years after LT; C and D: Trough concentrations of TAC (C) and CSA (D) grouped by combination with and without MMF at different time points. Patients with MMF combination had a lower calcineurin inhibitor trough concentrations but most without statistical significance. NS: Not significant.