HBV antiviral associated with progression of chronic kidney disease
The nucleotide analogue tenofovir disoproxil fumarate (TDF) is associated with mild renal impairment in a minority of patients being treated for chronic hepatitis B virus (HBV) infection, a study by the Chinese University of Hong Kong (CUHK) has shown.
The territory-wide retrospective cohort study included patients with chronic hepatitis B without treatment (n=2,254) or treated with TDF (n=2,254) or the nucleoside analogue entecavir (n=2,254). The patients were evaluated for chronic kidney disease (CKD) progression, defined as an increase of at least one CKD stage. [Aliment Pharmacol Ther 2018, doi: 10.1111/apt.14945]
The study, which used data from the Clinical Data Analysis and Reporting system (CDARS) of the Hong Kong Hospital Authority, showed that after a mean follow-up of 2.4 ± 1.5 years, the rate of CKD progression ≥1 stage was highest among patients who received TDF (31 percent) compared with those who received entecavir (28 percent) or those who did not receive any treatment (25 percent).
The patients’ mean baseline estimated glomerular filtration rate (eGFR) was 91.3 ± 20.6 mL/min/1.73 m2 in the TDF group, 90.3 ± 19.6 mL/min/1.73 m2 in the entecavir group, and 92.2 ± 20.0 mL/min/1.73 m2 in the untreated group.
“This large-scale study was the first to show TDF treatment significantly increased the risk of CKD progression vs entecavir. Lack of treatment for chronic hepatitis B, however, was also associated with a risk for CKD progression over time,” the authors commented. “This is likely because hepatitis B infection is known to cause CKD, such as membranous glomerulonephritis, in some patients.” [N Engl J Med 1991;324:1457-1463]
The 5‐year cumulative incidence of CKD progression was significantly higher in the TDF-treated group (48 percent; 95 percent confidence [CI] interval, 45 to 51; p<0.001) vs the entecavir-treated group (43 percent; 95 percent CI, 40 46; p=0.267) and the untreated group (43 percent; 95 percent CI, 39 to 47).
The mean annual change in eGFR vs the untreated cohort was also larger in TDF-treated patients (−0.62 mL/min/1.73 m2; 95 percent CI, −0.98 to −0.27; p=0.001) than in entecavir-treated patients (−0.27 mL/min/1.73 m2; 95 percent CI, −0.63 to 0.09; p=0.144).
“TDF use has been previously demonstrated to cause dose-dependent nephrotoxicity in both animal and human studies. Hence, renal function together with serum phosphate levels should be regularly monitored among patients receiving this treatment,” the authors suggested. [Antimicrob Agents Chemother 2008;52:3144-3160]
“Patients treated with TDF who are at risk of developing renal or bone disease should be considered for a switch to entecavir or tenofovir alafenamide [TAF],” they added.
TAF has demonstrated a better renal and bone safety profile compared with TDF. It is more stable than TDF in the plasma and can provide similar efficacy with lower circulating concentration in patients with HBV infection. [Expert Rev Gastroenterol Hepatol 2017;11:999-1008]
The CUHK group previously demonstrated that exposure to nucleotide analogues compared with nucleoside analogues was associated with an increased risk for hip fractures. [Hepatology 2015;62:684-693]