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替诺福韦酯富马酸盐和恩替卡韦联合乙型肝炎免疫球蛋白在肝移植患者中的肾脏安全性

Renal safety of tenofovir disoproxil fumarate and entecavir with hepatitis B immunoglobulin in liver transplant patients.

作者信息

Lee Juhan, Park Jun Yong, Yang Seok Jeong, Lee Jee Youn, Kim Deok Gie, Joo Dong Jin, Kim Myoung Soo, Kim Soon Il, Lee Jae Geun

机构信息

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

出版信息

J Viral Hepat. 2020 Aug;27(8):818-825. doi: 10.1111/jvh.13291. Epub 2020 Apr 17.

Abstract

Potent nucleos(t)ide analogues and hepatitis B immunoglobulin combinations are recommended after liver transplantation to prevent the recurrence of hepatitis B virus (HBV). Despite its proven efficacy, the renal safety of tenofovir disoproxil fumarate (TDF) has not been well established in liver transplant recipients. We aimed to assess the impacts of TDF and entecavir (ETV) on tubular and glomerular functions. We analysed 206 liver transplant patients treated with TDF (n = 102) or ETV (n = 104) plus hepatitis B immunoglobulin. Serum creatinine, phosphate and uric acid levels were measured. Proximal tubular dysfunction was defined as the presence of hypophosphatemia (<2 mg/dL) and hypouricemia (<2 mg/dL). Glomerular dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m accompanied by a ≥25% eGFR decline from baseline. During a median follow-up of 42.5 months, 48 patients developed proximal tubular dysfunction (30.4% and 16.3% in the TDF and ETV groups; P = .017). Serum levels of phosphate and uric acid were significantly lower in the TDF group post-LT. TDF (OR, 2.34; 95% CI, 1.16-4.69; P = .017) and low body mass index (OR, 2.11; 95% CI, 1.06-4.21; P = .034) were independent risk factors for proximal tubular dysfunction. The prevalence of glomerular dysfunction was not significantly different between the two groups (TDF 51.0% and ETV 54.8%; P = .582). TDF significantly increased the risk of proximal tubular dysfunction. Although the effect of TDF on glomerular function was comparable to that of ETV, glomerular dysfunction was common after liver transplant.

摘要

肝移植后推荐使用强效核苷(酸)类似物与乙型肝炎免疫球蛋白联合用药,以预防乙型肝炎病毒(HBV)复发。尽管富马酸替诺福韦二吡呋酯(TDF)已证实有效,但其在肝移植受者中的肾脏安全性尚未明确。我们旨在评估TDF和恩替卡韦(ETV)对肾小管和肾小球功能的影响。我们分析了206例接受TDF(n = 102)或ETV(n = 104)加乙型肝炎免疫球蛋白治疗的肝移植患者。测量血清肌酐、磷酸盐和尿酸水平。近端肾小管功能障碍定义为存在低磷血症(<2 mg/dL)和低尿酸血症(<2 mg/dL)。肾小球功能障碍定义为估计肾小球滤过率(eGFR)<60 mL/min/1.73 m²,且较基线水平eGFR下降≥25%。在中位随访42.5个月期间,48例患者出现近端肾小管功能障碍(TDF组和ETV组分别为30.4%和16.3%;P = 0.017)。肝移植后TDF组血清磷酸盐和尿酸水平显著降低。TDF(比值比,2.34;95%置信区间,1.16 - 4.69;P = 0.017)和低体重指数(比值比,2.11;95%置信区间,1.06 - 4.21;P = 0.034)是近端肾小管功能障碍的独立危险因素。两组间肾小球功能障碍的患病率无显著差异(TDF组为51.0%,ETV组为54.8%;P = 0.582)。TDF显著增加近端肾小管功能障碍的风险。尽管TDF对肾小球功能的影响与ETV相当,但肝移植后肾小球功能障碍很常见。

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