title: eGFR decrease during antiviral C therapy with first generation protease inhibitors: a clinical significance?
abstract: OBJECTIVE
  Renal toxicity of first generation protease inhibitors (PIs) was not a safety signal in phase III clinical trials, but was recently reported in recent studies. It appeared important to determine the clinical significance of these findings.
  
  
  METHODS
  We retrospectively analysed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n = 39) with peginterferon and ribavirin and having a close monitoring of eGFR (MDRD formula) during and after treatment. EGFR decline over time was assessed by a linear mixed-effects model (LMEM) with search for possible explanatory covariates.
  
  
  RESULTS
  Patients treated with telaprevir presented a significant decrease of eGFR with the same kinetics: initial decrease at W (week) 4, nadir at W8 (mean decrease 17.0 ± 18.9 ml/min/1.73 m(2)) and return to baseline at W16. The W8 eGFR was correlated with the D0 eGFR (R(2) = 0.49). The LMEM showed that interindividual variability in the slope of eGFR vs time between D0 and W8 was non-significant and eGFR nadir could be predicted from eGFR obtained at D0. In multivariate analysis, eGFR intercept (i.e. baseline value) was associated with older age and male sex.
  
  
  CONCLUSIONS
  The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir has been shown to inhibit mostly the drug transporter OCT2 which interacts with creatinine transport, the early decrease of eGFR observed could be a benign phenomenon. However, as unpredictable true renal toxicity may occur during therapy, we recommend a thorough follow-up of eGFR.
authors.affiliation: Service d'Hépato-gastroentérologie, CHU de Limoges, 2 avenue Martin-Luther-King, 87042, Limoges, France; Inserm UMR 1092, Faculté de médecine de Limoges, Université de Limoges, Limoges, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Loustaud-Ratti
authors.forename: Annick
authors.initials: A
authors.lastname: Rousseau
authors.forename: Paul
authors.initials: P
authors.lastname: Carrier
authors.forename: Chanlina
authors.initials: C
authors.lastname: Vong
authors.forename: Tristan
authors.initials: T
authors.lastname: Chambaraud
authors.forename: Jérémie
authors.initials: J
authors.lastname: Jacques
authors.forename: Marilyne
authors.initials: M
authors.lastname: Debette-Gratien
authors.forename: Denis
authors.initials: D
authors.lastname: Sautereau
authors.forename: Marie
authors.initials: M
authors.lastname: Essig
mesh_terms: D000367:Age Factors; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000378:metabolism*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin; D012737:Sex Factors
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D066246:ErbB Receptors; C100416:peginterferon alfa-2a
keywords: boceprevir; hepatitis C virus; renal impairment; telaprevir