富马酸替诺福韦二吡呋酯对乙型肝炎病毒感染孕妇肾功能的影响

Effect of tenofovir disoproxil fumarate on renal function in pregnant women with hepatitis B virus infection

目的探讨妊娠中晚期应用富马酸替诺福韦二吡呋酯(TDF)加强乙型肝炎病毒(HBV)母婴传播的阻断对孕妇肾功能的影响。方法研究对象选自在首都医科大学附属北京地坛医院妇产科建档并于2021年1—12月分娩的HBV感染孕妇。HBV DNA≥2.0×10^(5) IU/ml并在孕24~28周选择服用TDF治疗者纳入治疗组,HBV DNA<2.0×10^(5) IU/ml、孕期未使用抗HBV药物治疗者纳入对照组。收集2组孕妇的病历资料,包括孕24~28周(基线)的尿常规、肝功能、肾功能、估算肾小球滤过率(eGFR)、血磷、乙型肝炎血清标志物、HBV DNA等指标,以及孕36~37周、分娩时和产后42 d的肾功能、eGFR、血磷和肾小管损伤相关不良事件。比较2组孕妇在孕36~37周、分娩时和产后42 d的血清肌酐(Scr)、血尿素氮、eGFR和血磷的变化及治疗前后Scr和血磷的变化;记录治疗组肾小管相关不良事件发生情况。结果纳入分析的孕妇共189例,治疗组106例,对照组83例,2组孕妇的年龄、初产妇比例、基线丙氨酸转氨酶、Scr、血尿素氮、eGFR和血磷比较差异均无统计学意义(均P>0.05),治疗组HBeAg阳性者占比和HBV DNA水平均明显高于对照组(均P<0.05)。治疗组与对照组相比,孕36~37周、分娩时及产后42 d的Scr、血尿素氮、eGFR和血磷的差异均无统计学意义(均P>0.05)。从基线至产后42 d,Scr、血尿素氮、eGFR和血磷的变化趋势2组相似,差异均无统计学意义(均P>0.05)。治疗组孕妇无一例发生低磷血症、Scr升高、肾性低尿酸血症、β2微球蛋白尿、非糖尿病性糖尿和代谢性酸中毒等肾小管损伤相关不良事件。结论TDF在妊娠中晚期用于加强HBV母婴传播的阻断对肾脏是安全的。

Objective To explore the effect of tenofovir disoproxil fumarate(TDF)treatment on renal function for preventing mother-to-infant transmission of hepatitis B virus(HBV)in pregnant women during the second and third trimester of pregnancy.Methods The subjects were selected from pregnant women with HBV infection who were registered in Department of Gynecology and Obstetrics,Beijing Ditan Hospital,Capital Medical University and delivered between January and December 2021.The pregnant women who had HBV DNA≥2.0×10^(5) IU/ml and took TDF at 24-28 weeks of gestation were included in treatment group,and the pregnant women who had HBV DNA<2.0×10^(5) IU/ml and did not use anti-HBV drugs during pregnancy were included in control group.The medical records data of pregnant women in the 2 groups were collected,including urine routine examination,liver function,renal function,estimated glomerular filtration rate(eGFR),blood phosphorus,serum markers of hepatitis B,HBV DNA,ect.at 24-28 weeks of gestation(baseline data),renal function,eGFR,serum phosphorus at 36-37 weeks of gestation,delivery,and 42 days postpartum,and adverse events related to renal tubular injury.Serum creatinine(Scr),blood urea nitrogen,eGFR,and blood phosphorus at baseline level,36-37 weeks,delivery and 42 days postpartum,and changes of Scr and blood phosphorus before and after treatment between the 2 groups were compared,and adverse events related to renal tubular injury in the treatment group were recorded.Results A total of 189 pregnant women were entered in the analysis,including 106 in the treatment group and 83 in the control group.The differences in age,proportion of primipara,baseline level of alanine aminotransferase,Scr,blood urea nitro-gen,eGFR and blood phosphorus between the 2 groups were not statistically significant(all P>0.05),but the proportion of HBeAg-positive women and HBV DNA level in the treatment group were significantly higher than those in the control group(all P<0.05).The differences in Scr,blood urea nitrogen,eGFR,and blood phosphorus between the treatment group and the control group at 36-37 weeks of gestation,delivery and 42 days postpartum were not statistically significant(allP>0.05).The trends of changes in Scr,blood urea nitrogen,eGFR,and blood phosphorus from baseline level to 42 days postpartum were similar between 2 groups(all P>0.05).None of the pregnant women in the treatment group had adverse events related to renal tubular injury,such as hypophosphatemia,elevated Scr,renal hypouricemia,β2-microglobulinuria,non-diabetic glycosuria,metabolic acidosis,etc.Conclusion TDF is safe for the kidney in the second and third trimester of preg-nancy to strengthen the blocking of mother-to-infant transmission of HBV.