Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People's Republic of China.
Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital, Logistics University of People's Armed Police Force, 220 Chenglin Road, Hedong District, Tianjin, 300162, People's Republic of China.
Int Urol Nephrol. 2019 Apr;51(4):677-690. doi: 10.1007/s11255-019-02110-8. Epub 2019 Mar 4.
Hepatitis B virus (HBV) infection is a public health challenge, especially in China. In clinical practice, HBV infection is associated with nephropathy. Impaired renal function is frequently observed in compensated Chronic Hepatitis B (CHB) and cirrhosis (LC). Thus, renal function must be monitored to avoid nephrotoxic effects before and during nucleoside analog treatment. Investigating the predictive markers of early renal dysfunction is essential. New GFR-predicting equations, based on Pcr and/or CystC, have been recently recommended in the general population, but their performance in liver disease patients has been rarely studied. In this study, we will discuss how to detect renal dysfunction in patients with HBV infection.
A total of 16 LC patients and 23 CHB patients were enrolled in this study, and we collected and compared the clinical data of the two groups. The estimated glomerular filtration rates (eGFRs) were also calculated by several equations. All patients received 99mTc-DTPA dynamic radionuclide imaging examinations to obtain mGFRs as the reference standard. To evaluate the performance of any equation in the CHB and LC groups, paired t test, Pearson's correlation, Kappa analysis and Bland-Altman plots were utilized. Moreover, all 39 subjects were divided into two groups (according to GFR > 90 mL/min/1.73 m). We compared the serum and urinary markers of kidney injury between the two groups and selected the indicators of renal injury by univariate analysis.
The mGFR was 72.26 ± 20.69 mL/min/1.73 m in the LC group, and 87.49 ± 25.91 mL/min/1.73 m in the CHB group. The paired t test results of eGFR and mGFR showed no difference between eGFR (estimated by the CHINAcr-cys equation) and mGFR (p > 0.05) in the compensated LC and CHB groups. The difference between mGFR and eGFR estimated by other methods was obvious (p < 0.05). Comparing the eGFRs (estimated by 5 different equations) with mGFR in the compensated LC and CHB groups, Pearson's correlation showed that only eGFR (estimated by the CHINAcr-cys equation) had a significant correlation coefficient in CHB (r = 0.678, p = 0.000) and had the highest R (R = 0.459) among all other measures. The kappa consistency test showed that eGFR from CHINAscr-cys had poor consistency with mGFR in the compensated LC group but moderate consistency in the CHB group. Bland-Altman consistency analysis showed that in the CHB group, the CHINAcr-cys and CKD-EPIcr equations presented narrower acceptable limits than did the aMDRD, c-aMDRD, and CKD-EPIcr-cys equations (62.8, 56.1 vs .85.7, 102.9, 93.6 mL/min per 1.73 m). In the compensated LC group, the CHINAcr-cys and CKD-EPIcr equations presented narrower acceptable limits than did the aMDRD, c-aMDRD, and CKD-EPIcr-cys equations (83.6, 81.3 vs. 98, 113.5, 106.3 mL/min per 1.73 m). Serum or urinary markers were compared with renal function (GFR > 90 mL/min/1.73 m) and showed International normalized ratio (INR) (p = 0.009), creatinine (p = 0.006), urine N-acetyl-β-glucosaminidase (NAG) (p = 0.001) and serum cystatin C (CysC) (p = 0.044).
The CHINAcr-cys equation may be more suitable for the estimation of GFR in Chinese patients with CHB or compensated cirrhosis. INR, creatinine, NAG, and CysC are proper biomarkers for screening renal dysfunction in Chinese patients with CHB or compensated LC.
乙型肝炎病毒(HBV)感染是一个公共卫生挑战,尤其是在中国。在临床实践中,HBV 感染与肾病有关。代偿性慢性乙型肝炎(CHB)和肝硬化(LC)患者常伴有肾功能损害。因此,在核苷类似物治疗前和治疗期间,必须监测肾功能以避免肾毒性作用。探讨早期肾功能障碍的预测标志物至关重要。新的基于 Pcr 和/或 CystC 的肾小球滤过率(GFR)预测方程最近已在普通人群中推荐,但在肝病患者中的性能研究较少。在本研究中,我们将讨论如何检测 HBV 感染患者的肾功能障碍。
本研究共纳入 16 例 LC 患者和 23 例 CHB 患者,收集并比较了两组患者的临床资料。采用多种方程计算估计肾小球滤过率(eGFR)。所有患者均接受 99mTc-DTPA 动态放射性核素成像检查,以获得 mGFR 作为参考标准。为了评估任何方程在 CHB 和 LC 组中的性能,采用配对 t 检验、Pearson 相关分析、Kappa 分析和 Bland-Altman 图进行分析。此外,所有 39 名受试者被分为两组(根据 GFR>90mL/min/1.73m)。我们比较了两组患者的血清和尿肾损伤标志物,并通过单因素分析选择肾损伤指标。
LC 组 mGFR 为 72.26±20.69mL/min/1.73m,CHB 组 mGFR 为 87.49±25.91mL/min/1.73m。LC 和 CHB 组代偿期 eGFR(由 CHINAcr-cys 方程估算)与 mGFR 的配对 t 检验结果无差异(p>0.05)。其他方法估算的 mGFR 与 eGFR 之间的差异明显(p<0.05)。比较代偿性 LC 和 CHB 组中 5 种不同方程估算的 eGFR 与 mGFR,Pearson 相关分析显示,仅 CHB 组中 eGFR(由 CHINAcr-cys 方程估算)的相关系数有显著意义(r=0.678,p=0.000),且在所有其他测量方法中相关性最高(R=0.459)。Kappa 一致性检验显示,LC 组中 CHINAscr-cys 的 eGFR 与 mGFR 一致性较差,而 CHB 组中一致性较好。Bland-Altman 一致性分析显示,在 CHB 组中,CHINAcr-cys 和 CKD-EPIcr 方程的可接受范围较窄,而 aMDRD、c-aMDRD 和 CKD-EPIcr-cys 方程的可接受范围较宽(62.8、56.1 vs.85.7、102.9、93.6mL/min/1.73m)。在代偿性 LC 组中,CHINAcr-cys 和 CKD-EPIcr 方程的可接受范围较窄,而 aMDRD、c-aMDRD 和 CKD-EPIcr-cys 方程的可接受范围较宽(83.6、81.3 vs.98、113.5、106.3mL/min/1.73m)。将血清或尿液标志物与肾功能(GFR>90mL/min/1.73m)进行比较,结果显示国际标准化比值(INR)(p=0.009)、肌酐(p=0.006)、尿 N-乙酰-β-氨基葡萄糖苷酶(NAG)(p=0.001)和血清胱抑素 C(CysC)(p=0.044)与肾功能相关。
CHINAcr-cys 方程可能更适合于中国 CHB 或代偿性肝硬化患者的 GFR 估计。INR、肌酐、NAG 和 CysC 是筛查中国 CHB 或代偿性 LC 患者肾功能障碍的合适生物标志物。