The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists

Abstract

Tenofovir is a nucleotide acting both as an inhibitor of human immunodeficiency (HIV) reverse transcriptase and as a competitor for hepatitis B virus (HBV) RNA-directed DNA polymerase. Approved worldwide in 2001, tenofovir is used as a component of highly active antiretroviral therapy (HAART) in patients with HIV infection. Since 2008, it has also been indicated for treatment of chronic HBV infection or HIV/HBV co-infection. The aim of the treatment consists in suppressing viral replication, thus reducing hepatic complications and improving patient survival. Furthermore, tenofovir could represent an effective therapeutic option in lamivudine-resistant HBV patients. Tenofovir is eliminated unchanged through urine via glomerular filtration (80%) and proximal tubular secretion (20%). Thus, alterations in renal clearance may interfere with tenofovir pharmacokinetics and systemic drug concentrations, modifying the therapeutic response. Hence, a renal overload of tenofovir in patients with a pre-existing kidney impairment could result in a worsening of renal function. Following a brief introduction on HBV infection and its therapeutic options, we review the latest evidence, to our knowledge, on renal toxicity of tenofovir in HBV patients and on drug management.

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…In addition, studies using sensitive markers of glomerular and tubular kidney function and of bone mineral density have also reported chronic tubular damage and decline of eGFR and bone mineral density in TDF treated patients. 70,[79][80][81][82][83][84][85][86][87] Therefore, it seems appropriate for now to monitor all CHB patients treated with TDF therapy for adverse renal effects with serum creatinine (eGFR) and serum phosphate levels. Moreover, CHB patients at high renal risk undergoing any NA therapy should be monitored with serum creatinine (eGFR) levels.…”

Long‐term safety and efficacy of tenofovir disoproxil fumarate substitution for hepatitis B immunoglobulin following liver transplantation

“…The high rates of renal dysfunction may partially be explained by more known risk factors for renal dysfunction in the affected subjects, such as older age (median 64 years), a lower baseline creatinine clearance compared to the rest of the cohort (48.5 μmol/L vs 73 μmol/L), concomitant CNI use (50%), diabetes mellitus (50%), and hypertension (67%). The proportion of renal dysfunction attributable to TDF alone is unable to be assessed by our study given that other nephrotoxic therapies were adjusted or ceased following the identification of renal dysfunction.…”

Monotherapy for hepatitis B infection: a review of treatment options

“…Tenofovir is eliminated unchanged through urine through glomerular filtration (80%) and proximal tubular secretion (20 %) [80]. For this reason, alterations in renal functions may influence pharmacokinetics and systemic drug concentrations of tenofovir and modifying the therapeutic response.…”