Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease

Abstract

Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n = 60) and telbivudine-replacement (n = 60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p < 0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.

Figures

Figure 1

The flow diagram of 120 patients enrolled in this study. Each arm consisted of 60 patients. Two patients in LAM-C arm and 6 patients in LdT-R arm were withdrawn. Finally, 58 patients in LAM-C arm and 54 patients in LdT-R arm completed the study.

Figure 2

The trough levels of tacrolimus during the study. The trough blood levels of tacrolimus were 4.90 ± 1.85 in LAM-C group and 4.89 ± 2.22 ng/ml in LdT-R group when the patients were enrolled in the study (p = 0.588). During the study, trough levels of tacrolimus were slightly declined. At the end of this study, the trough blood levels of tacrolimus were 4.21 ± 1.67 ng/ml in LAM-C group and 3.87 ± 1.51 ng/ml in LdT-R group (p = 0.317).

Figure 3

The eGRF for the patients in the two arms. At the beginning, the baseline eGRF of LdT-R arm patients was 63.0 ± 16.3 ml/min which was not different from 61.6 ± 16.8 ml/min of LAM-C arm patients (p = 0.645). The renal function was improved for the patients in LdT-R arm from 10 months after LdT administration and reached 72.8 ± 21.1 ml/min at 12 months (p = 0.003).

Figure 4

The eGRF for the patients with renal function in stage II or III. (a) For the 32 patients in stage II in LdT-R arm, eGRF was improved from baseline 74.7 ± 6.9 ml/min to 79.7 ± 8.7 ml/min at 10 months of LdT administration (p = 0.007) and 84.2 ± 16.6 ml/min at 12 months of LdT administration (p = 0.002). Compared to LAM-C arm, eGFR became different from 10 months after LdT administration. (b) For the 20 patients in stage III, eGRF was improved from baseline 48.2 ± 7.3 ml/min to 54.4 ± 14.1 ml/min at 10 months of LdT administration (p = 0.002) and 59.7 ± 11.8 ml/min at 12 months of LdT administration (p < 0.001). Compared to LAM-C arm, eGFR became improved at 12 months after LdT administration.

Figure 5

The change of eGFR for an individual patient between initiation and end of the study. (a) In LAM-C arm, 32 (55.2%) patients had better eGFR, 23 (39.6%) patients had worse eGFR, and 3 (5.2%) patients did not have any change. Among them, 22 (37.9%) patients had their eGFR improvement ≥4 ml/min. (b) In LdT-R arm, 44 (81.5%) patients had better eGFR and 10 (18.5%) patients had worse eGFR. Among them, 37 (68.5%) patients had their eGFR improvement ≥4 ml/min.

Figure 6

The relationship between alternation of tacrolimus and eGFR at the end of the study. (a) In LAM-C arm, the alternation of eGFR was not correlated to the alternation of tacrolimus trough levels (R2 = 0.0183). (b) In LdT-R arm, the alternation of eGFR was not correlated to the alternation of tacrolimus trough levels, either (R2 = 0.0119).

Figure 7

The eGFR for the patients in LdT arm and switched back to LAM. During post hoc following-up, 9 patients had polyneuropathy and were switched back to LAM. While LdT was switched back to LAM, eGFR was kept in improved renal function in 5 (55.6%) patients and returned to original levels in 4 (44.4%) patients.