title: Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.
abstract: OBJECTIVE
  Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir.
  
  
  METHODS
  We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2).
  
  
  RESULTS
  During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline.
  
  
  CONCLUSIONS
  In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy p_maggi@yahoo.com.
authors.forename: Paolo
authors.initials: P
authors.lastname: Maggi
authors.affiliation: Institute of Nephrology, Policlinico-University of Bari, Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Montinaro
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Leone
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Volpe
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellacosa
authors.affiliation: Institute of Rheumatology, Policlinico-University of Bari, Bari, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Grattagliano
authors.affiliation: Institute of Rheumatology, Policlinico-University of Bari, Bari, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Coladonato
authors.affiliation: Institute of Rheumatology, Policlinico-University of Bari, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Foggia, Foggia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.affiliation: Institute of Infectious Diseases, Policlinico-University of Bari, Bari, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Angarano
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001847:Bone Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005919:Glomerular Filtration Rate; D006417:Hematuria / Q000139:chemically induced / Q000453:epidemiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced / Q000453:epidemiology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000473:pathology; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria / Q000139:chemically induced / Q000453:epidemiology; D014808:Vitamin D Deficiency / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine
keywords: adefovir; bone toxicity; hepatitis B; tenofovir