title: Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B.
abstract: OBJECTIVE
  To evaluate urine β2-microglobulin (β2-M), retinol-binding protein (RBP) excretion, and renal impairment with adefovir dipivoxil (ADV) for chronic hepatitis B.
  
  
  METHODS
  We enrolled 165 patients with chronic hepatitis B infection who were treated with ADV monotherapy (n = 90) or ADV plus lamivudine combination therapy (n = 75). An additional 165 chronic hepatitis B patients treated with entecavir were recruited as controls. We detected serum creatinine, urine β2-M, and RBP levels, and estimated the glomerular filtration rate (eGFR) at the initiation of antiviral therapy and every 6 mo for a period of five years.
  
  
  RESULTS
  Urine β2-M abnormalities were observed in patients during the first (n = 3), second (n = 7), third (n = 11), fourth (n = 16), and fifth (n = 21) year of ADV treatment. Urinary RBP abnormalities were observed in patients during the first (n = 2), second (n = 8), third (n = 12), fourth (n = 15), and fifth (n = 22) year of ADV treatment. eGFR decreased 20%-30% from baseline in 20 patients, 30%-50% in 12 patients, and > 50% in 3 patients during the five years of treatment. Further analysis indicated that decreases in eGFR of ≥ 30% relative to the baseline level correlated significantly with urine RBP and β2-M abnormalities. In contrast, both serum creatinine and eGFR remained stable in patients treated with entecavir, and only one of these patients developed a urine β2-M abnormality, and two developed urine RBP abnormalities during the five years of treatment.
  
  
  CONCLUSIONS
  Urine RBP and β2-M are biomarkers of renal injury during long-term ADV treatment for chronic hepatitis B, and indicate when treatment should be switched to entecavir.
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Jia
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jiang-Shan
authors.initials: JS
authors.lastname: Lian
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Lin-Yan
authors.initials: LY
authors.lastname: Zeng
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Dai-Rong
authors.initials: DR
authors.lastname: Xiang
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Hu
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Yu
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Li
authors.affiliation: Hong-Yu Jia, Feng Ding, Jian-Yang Chen, Jiang-Shan Lian, Yi-Min Zhang, Lin-Yan Zeng, Dai-Rong Xiang, Liang Yu, Jian-Hua Hu, Guo-Dong Yu, Huan Cai, Ying-Feng Lu, Lin Zheng, Lan-Juan Li, Yi-Da Yang, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Yi-Da
authors.initials: YD
authors.lastname: Yang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D057915:Drug Substitution; D005260:Female; D005919:Glomerular Filtration Rate; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012177:Retinol-Binding Proteins / Q000652:urine; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D063065:Organophosphonates; D012177:Retinol-Binding Proteins; D001613:beta 2-Microglobulin; C413685:entecavir; D006147:Guanine; D003404:Creatinine; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Adefovir dipivoxil; Entecavir; Renal impairment; Retinol binding protein; Urine β2-microglobulin
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