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 ear...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.展开更多
利率(国家间的利差)如果上升,债务就会依据经济基本面的情况,自发产生滚雪球效应。这是市场的一个不完美之处,因为我们不能确保市场自身会远离“差的”均衡而达到“好的”均衡。我们提出了一个政策干预机制来解决国际间资本流动的结构...利率(国家间的利差)如果上升,债务就会依据经济基本面的情况,自发产生滚雪球效应。这是市场的一个不完美之处,因为我们不能确保市场自身会远离“差的”均衡而达到“好的”均衡。我们提出了一个政策干预机制来解决国际间资本流动的结构性弱点。这个政策干预机制的基础是一个简单的分类,它把危机的根源分为三种:信心(利差和货币危机)、基本面(实际增长率)和经济政策(初始赤字)。然后,从理论上提出了“第一贷款人”(lender of first resort,以下简称LFR)适用的一些环境。本文提出的政策机制希望通过IMF的一些支持来增强事前激励,从而化解避免危机。本文还介绍了“集体行动条款”(collective action clauses---CACs)在减少自我实现性债务危机(self-fullfilling debtcrises,文中有时也翻译为自发性债务危机)中的潜在作用。展开更多
文摘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.
文摘利率(国家间的利差)如果上升,债务就会依据经济基本面的情况,自发产生滚雪球效应。这是市场的一个不完美之处,因为我们不能确保市场自身会远离“差的”均衡而达到“好的”均衡。我们提出了一个政策干预机制来解决国际间资本流动的结构性弱点。这个政策干预机制的基础是一个简单的分类,它把危机的根源分为三种:信心(利差和货币危机)、基本面(实际增长率)和经济政策(初始赤字)。然后,从理论上提出了“第一贷款人”(lender of first resort,以下简称LFR)适用的一些环境。本文提出的政策机制希望通过IMF的一些支持来增强事前激励,从而化解避免危机。本文还介绍了“集体行动条款”(collective action clauses---CACs)在减少自我实现性债务危机(self-fullfilling debtcrises,文中有时也翻译为自发性债务危机)中的潜在作用。
