Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B.

Abstract

BACKGROUND:

Renal dysfunction and Fanconi's syndrome associated with hypophosphatemia caused by long-term administration of low-dose adefovir dipivoxil (ADV) has been reported in recent years. The aim of this retrospective study was to determine the incidence and factors associated with renal dysfunction and hypophosphatemia in patients with hepatitis B infection on long-term treatment with ADV and lamivudine (LAM).

METHODS:

The study subjects were 292 patients treated with 10 mg/day ADV and 100 mg/day LAM for more than 6 months. We evaluated estimated glomerular filtration rate (eGFR), serum creatinine and serum phosphate level at the start of ADV and every 6 months.

RESULT:

During a median treatment duration of 64 months, 28 (9.6 %) patients developed renal impairment (defined as eGFR < 50 ml/min/1.73 m(2)), and 73 (27.1 %) developed hypophosphatemia, including 14 with persistent hypophosphatemia. The cumulative incidences of renal impairment at 1, 3, and 5 years were 1.4, 7.5, 10.5 %, respectively, and those of hypophosphatemia were 6.8, 20.6, 26.7 %, respectively. Multivariate analysis identified old age, liver cirrhosis and hypertension as determinants of renal impairment, and male sex, HCC, low baseline serum phosphate as determinants of hypophosphatemia. Three of the 14 patients with persistent hypophosphatemia developed Fanconi's syndrome; their serum creatinine level remained normal, but eGFR was lower than at baseline.

CONCLUSION:

Long-term treatment of hepatitis B with low-dose (10 mg/day) ADV and LAM can potentially cause renal impairment and hypophosphatemia. We advocate regular monitoring of serum phosphate and evaluation of eGFR, in addition to serum creatinine, in such patients.

• Authors: Mio Tanaka, Fumitaka Suzuki, Yuya Seko, Tasuku Hara, Yusuke Kawamura, Hitomi Sezaki, Tetsuya Hosaka, Norio Akuta, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 49 Issue 3 Pg. 470-80 (Mar 2014) ISSN: 1435-5922 [Electronic] Japan
• PMID: 23525978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Organophosphonates
• Lamivudine
• Creatinine
• Adenine
• adefovir dipivoxil

Topics

• Adenine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects, therapeutic use)
• Creatinine (blood)
• Drug Therapy, Combination
• Female
• Glomerular Filtration Rate
• Hepatitis B, Chronic (drug therapy)
• Humans
• Hypophosphatemia (chemically induced, epidemiology)
• Incidence
• Kidney Diseases (chemically induced, epidemiology)
• Lamivudine (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Multivariate Analysis
• Organophosphonates (administration & dosage, adverse effects, therapeutic use)
• Retrospective Studies
• Risk Factors
• Time Factors