Impact of nucleos(t)ide analogue combination therapy on the estimated glomerular filtration rate in patients with chronic hepatitis B

Abstract

Monotherapy with telbivudine or adefovir can affect estimated the glomerular filtration rate (eGFR). However, only a few studies have assessed changes in eGFR in patients who have chronic hepatitis B (CHB) and are receiving nucleos(t)ide analogue (NA) combination therapy. In our study, we aimed to evaluate the effects of long-term NA combination therapy on eGFR in Chinese CHB patients. This retrospective study included 195 CHB patients. Patient subgroups included those treated with lamivudine plus adefovir (n = 73), telbivudine plus adefovir (n = 51), and entecavir plus adefovir (n = 35); untreated patients (n = 36) served as a control group. After an average follow-up duration of 24 months with combination therapy, analysis of changes in eGFR from baseline values, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulas, showed decrease by 11.08 and 18.34 mL/min (P < .001), respectively, in the lamivudine plus adefovir group; decrease by 3.73 and 10.04 mL/min (P = .012), respectively, in the entecavir plus adefovir group; and increase by 0.91 and 2.12 mL/min (P = .46), respectively, in the telbivudine plus adefovir group. The eGFR in the telbivudine plus adefovir group was similar to that for the untreated group. The eGFR decreases due to adefovir therapy could be rescued by adding telbivudine, and the eGFR increase due to telbivudine could be compromised by adding adefovir. Adefovir in combination with lamivudine or entecavir therapy was significantly associated with decreased eGFR, but telbivudine could rescue the eGFR decrease that results from adefovir treatment.

FIGURE 1

Changes in renal function-associated indicators during follow-up in patients treated with different NA combination therapies. (A) Serum creatinine; (B) eGFR calculated by the MDRD equation; (C) eGFR calculated by the CKD-EPI equation.

FIGURE 2

Changes in the eGFR of patients after each NA combination therapy.

FIGURE 3

Changes in the eGFR at week 104 in patients with and without mild renal impairment at baseline. eGFRcalculated by (A) the MDRD equation and (B) the CKD-EPI equation.^∗P < 0.05, ^∗∗P < 0.01, ^∗∗∗P < 0.001.

FIGURE 4

Changes in eGFR (MDRD) in patients who shifted from monotherapy to combination therapy. (A) Patients who did not achievevirological response after receiving adefovir treatment. (B) Patients who showed resistance to NAs.