Division of Nephrology, University of Medicine and Pharmacy V. Babes Timisoara, Romania.
Immunopharmacol Immunotoxicol. 2011 Dec;33(4):744-50. doi: 10.3109/08923973.2010.551129. Epub 2011 Feb 14.
HBV and HCV chronic hepatitis can be accompanied by secondary renal disease. In addition, these patients receive antiviral drugs with potential nephrotoxicity. It is known that interferon (IFN) therapy in HCV-infected kidney transplant recipients is followed by rejection of the transplant in 50% of the cases. Ribavirin is contraindicated in hemodialyzed patients and in patients with a GFR <50 ml/min/1.73 m(2). IFN therapy requires dosage reduction and close monitoring in patients with a GFR <50 ml/min/1.73 m(2) and in patients with end stage renal disease. The aim of our study was to assess the nephrotoxicity of antiviral drugs in patients with chronic hepatitis by measuring three renal biomarkers: urinary albumin, N-acetyl-β-D-glucosaminidase (NAG) and α 1-microglobulin, as well as glomerular filtration rate (GFR-MDRD4) before and at 6 months of therapy.
Fifty-five patients (28 male and 27 female, with a mean age of 47.85 ± 12.03 years) with chronic hepatitis (40 patients with HCV, 13 patients with HBV, 1 patient with HBV+HCV, and 1 patient with HBV+HDV) were enrolled into the study. Different antiviral drug associations were used on a case-by-case basis. The 40 patients with HCV chronic hepatitis received either Peg-IFN-α 2a+Ribavirin (37 patients) or Peg-IFN-α 2b+Ribavirin (3 patients). The 13 patients with HBV chronic hepatitis received Peg-IFN-α 2a (9 patients), Lamivudine (2 patients), Entecavir (1 patient), or Adefovir (1 patient). The patient with HBV+HCV chronic hepatitis received Peg-IFN-α 2a+Ribavirin. The patient with HBV+HDV chronic hepatitis received IFN-α 2a. Urinary albumin (ELISA), NAG (colorimetrical method), α 1-microglobulin (ELISA), and serum creatinine were measured before and at 6 months of antiviral therapy. Urinary markers were expressed as either mg/gCr (for albumin and α 1-microglobulin) or U/gCr (for NAG). Statistical analysis (Pearson's correlation coefficient, paired t-test and χ(2)-test) was performed.
At 6 months of therapy urinary albumin/gCr did not increase significantly: 16.58 ± 23.39 vs. 15.85 ± 24.96 mg/gCr before therapy, p = 0.87. Urinary NAG/gCr did not increase significantly: 4.21 ± 3.37 vs. 3.83 ± 3.2 U/gCr before therapy, p = 0.53. Urinary α 1-microglobulin/gCr was almost unchanged: 4.38 ± 4.47 vs. 4.38 ± 3.57 mg/gCr before therapy, p = 0.99. The GFR did not decline significantly: 92.41 ± 22.21 vs. 94.59 ± 36.1 ml/min/1.73 m(2) before therapy, p = 0.7. Ten patients (18.18%) were albuminuric before therapy, and 14 patients (25.45%) were albuminuric at 6 months of therapy, a non-significant increase (p = 0.35). We found a correlation between urinary albumin/gCr and NAG/gCr and between urinary albumin/gCr and α 1-microglobulin/gCr both at baseline and at 6 months of therapy: r = 0.54, p = 0.0005; r = 0.29, p = 0.03; r = 0.51, p = 0.0005; and r = 0.4, p = 0.002, respectively. In the patient receiving Adefovir, a known nephrotoxic drug, two of the three biomarkers (urinary albumin/gCr and NAG/gCr) increased, most notably NAG/gCr. Both HCV and HBV chronic hepatitis therapy were associated with non-significant changes in renal biomarker excretion and GFR.
With the exception of Adefovir, all of the drug associations used in this study were safe.
HBV 和 HCV 慢性肝炎可伴有继发性肾病。此外，这些患者接受具有潜在肾毒性的抗病毒药物治疗。已知 HCV 感染的肾移植受者接受干扰素 (IFN) 治疗后，50%的患者会出现移植排斥反应。利巴韦林禁用于血液透析患者和肾小球滤过率 (GFR) <50 ml/min/1.73 m²的患者。IFN 治疗需要在 GFR <50 ml/min/1.73 m²和终末期肾病患者中减少剂量并密切监测。我们研究的目的是通过测量三种肾生物标志物（尿白蛋白、N-乙酰-β-D-氨基葡萄糖苷酶 (NAG) 和 α 1-微球蛋白）以及肾小球滤过率 (MDRD4)，在治疗前和治疗 6 个月时评估慢性乙型肝炎患者抗病毒药物的肾毒性。
55 例（28 名男性和 27 名女性，平均年龄 47.85 ± 12.03 岁）慢性乙型肝炎患者（40 例 HCV 患者、13 例 HBV 患者、1 例 HBV+HCV 患者和 1 例 HBV+HDV 患者）入组本研究。根据具体情况使用不同的抗病毒药物联合治疗。40 例 HCV 慢性肝炎患者接受 Peg-IFN-α 2a+利巴韦林（37 例）或 Peg-IFN-α 2b+利巴韦林（3 例）治疗。13 例 HBV 慢性肝炎患者接受 Peg-IFN-α 2a（9 例）、拉米夫定（2 例）、恩替卡韦（1 例）或阿德福韦（1 例）治疗。1 例 HBV+HCV 慢性肝炎患者接受 Peg-IFN-α 2a+利巴韦林治疗。1 例 HBV+HDV 慢性肝炎患者接受 IFN-α 2a 治疗。在抗病毒治疗前和 6 个月时测量尿白蛋白（ELISA）、NAG（比色法）、α 1-微球蛋白（ELISA）和血清肌酐。尿标志物分别以 mg/gCr（白蛋白和α 1-微球蛋白）或 U/gCr（NAG）表示。进行了统计学分析（Pearson 相关系数、配对 t 检验和 χ²检验）。
治疗 6 个月时，尿白蛋白/gCr 无明显增加：16.58 ± 23.39 比治疗前 15.85 ± 24.96 mg/gCr，p = 0.87。尿 NAG/gCr 无明显增加：4.21 ± 3.37 比治疗前 3.83 ± 3.2 U/gCr，p = 0.53。尿α 1-微球蛋白/gCr 几乎不变：4.38 ± 4.47 比治疗前 4.38 ± 3.57 mg/gCr，p = 0.99。肾小球滤过率无明显下降：92.41 ± 22.21 比治疗前 94.59 ± 36.1 ml/min/1.73 m²，p = 0.7。10 例（18.18%）患者治疗前白蛋白尿，14 例（25.45%）患者治疗 6 个月时白蛋白尿，增加不明显（p = 0.35）。我们发现治疗前和治疗 6 个月时尿白蛋白/gCr 与 NAG/gCr 以及尿白蛋白/gCr 与 α 1-微球蛋白/gCr 之间存在相关性：r = 0.54，p = 0.0005；r = 0.29，p = 0.03；r = 0.51，p = 0.0005；r = 0.4，p = 0.002，分别。在接受阿德福韦治疗的患者中，这是一种已知的肾毒性药物，两种生物标志物（尿白蛋白/gCr 和 NAG/gCr）均升高，尤其是 NAG/gCr。HCV 和 HBV 慢性肝炎治疗均与肾生物标志物排泄和肾小球滤过率的无显著性变化相关。
除阿德福韦外，本研究中使用的所有药物联合治疗均安全。
