摘要
BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple early markers are available,but no consensus exists on their use.AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy(SPT),as defined with early biomarkers,in treated vs untreated hepatitis B virus(HBV)-monoinfected patients.METHODS A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted.The patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)treatment.Data on the early markers of SPT,the eGFR and phosphatemia,were collected quarterly.SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%.The prevalence and cumulative incidence of SPT at month 24(M24)were calculated.Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data.Multivariate analyses were used to adjust for any potential confounding factors.RESULTS Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at inclusion.At M24,the prevalence of SPT was not statistically different between naïve and either treated group(21.1%vs 30.7%,P<0.42 and 50.0%vs 30.7%,P=0.32 for ETV and TDF,respectively);no patient had an eGFR lower than 50 mL/min/1.73 m²or phosphatemia less than 0.48 mmoL/L.In the multivariate analysis,no explanatory variables were identified after adjustment.The cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TDF groups,respectively.The median survival time without SPT,evaluated only in the TDF group,was 5.9 mo.CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients.SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
作者简介
Corresponding author:Veronique Loustaud-Ratti,MD,PhD,Professor,U1248 INSERM,Department of Hepatology and Gastroenterology,Univ.Limoges,CHU Limoges,2,Avenue Martin Luther King,Limoges F-87000,France.veronique.loustaud-ratti@unilim.fr.Veronique Loustaud-Ratti 0000-0002-6951-0784;ORCID number:Anais Brayette 0000-0003-2253-8111;Marie Essig 0000-0002-2030-5616;Paul Carrier 0000-0001-9750-2506;Marilyne Debette-Gratien 0000-0001-6039-1355;Anais Labrunie 0000-0002-3285-8015;Sophie Alain 0000-0002-9787-1421;Marianne Maynard 0000-0001-9172-7050;Nathalie Ganne-Carrie0000-0002-7351-5027;Eric Nguyen-Khac 0000-0001-8672-4146;Pauline Pinet 0000-0001-9259-6857;Victor De Ledinghen 0000-0001-6414-1951;Christophe Renou 0000-0002-5834-2391;Philippe Mathurin 0000-0003-3447-2025;Claire Vanlemmens 0000-0002-2048-3324;Vincent Di Martino 0000-0002-2022-690X;Anne Gervais 0000-0001-8593-6083;Juliette Foucher 0000-0003-2712-7469;Fouchard-Hubert Isabelle 0000-0002-7420-7026;Julien Vergniol 0000-0002-1109-1636;Isabelle Hourmand-Ollivier 0000-0002-5254-2464;Daniel Cohen 0000-0001-7461-6375;Xavier Duval 0000-0003-1079-4230;Thierry Poynard 0000-0002-2050-640X;Marc Bardou 0000-0003-0028-1837;Armand Abergel 0000-0001-7480-1052;Manh-Thong Dao 0000-0001-7043-4662;Thierry Thevenot 0000-0003-3974-2784;Jean-Baptiste Hiriart 0000-0002-8863-8230;Valerie Canva 0000-0003-4364-8133;Guillaume Lassailly 0000-0002-6955-244X;Christine Aurieres 0000-0003-4732-104X;Nathalie Boyer 0000-0003-1873-1701;Dominique Thabut 0000-0002-9658-0323;Pierre-Henri Bernard 0000-0003-0154-0722;Matthieu Schnee 0000-0001-6152-405X;Dominique Larrey 0000-0002-0892-3489;Bertrand Hanslik 0000-0002-1803-0799;Severine Hommel 0000-0001-7335-4772;Jeremie Jacques 0000-0003-4105-6804。
