基于 dolutegravir 的 ART 治疗的 HIV-1 感染患者中，血浆胱抑素 C 作为估计肾小球滤过率评估的标志物。

Plasma cystatin C as a marker for estimated glomerular filtration rate assessment in HIV-1-infected patients treated with dolutegravir-based ART.

机构信息

Infectious Diseases Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France.

Pierre Louis Institute of Epidemiology and Public Health (IPLESP, UMRS 1136), Paris, France.

出版信息

J Antimicrob Chemother. 2018 Jul 1;73(7):1935-1939. doi: 10.1093/jac/dky112.

DOI:10.1093/jac/dky112

PMID:29688533

Abstract

OBJECTIVES

Inhibition of the organic cation transporter-2 renal tubule transporter by dolutegravir leads to serum creatinine increase. Serum cystatin C is a non-organic cation transporter-2-dependent marker, possibly enabling glomerular filtration rate (GFR) estimation under dolutegravir. Our goal was to evaluate the changes in creatinine- and cystatin C-based estimated GFR values before and after dolutegravir initiation.

METHODS

Creatinine and cystatin measurements were carried out on frozen plasma samples from HIV-1-infected patients, before and after dolutegravir initiation, between October 2016 and March 2017 at Pitié-Salpêtrière Hospital. CKD-EPI equations were used to estimate mean GFR from creatinine and cystatin C values. Variations were analysed by paired t-test.

RESULTS

Forty-four patients were included [median age = 48 years (IQR 36-58) and median CD4 count = 592 cells/mm3 (IQR 388-728)], including 6 ART-naive patients and 38 on switch strategies [72% with viral load <50 copies/mL and median ART duration = 13 years (IQR 5-20)]. Before dolutegravir initiation (median time = 41 days), 19 patients (43%) had creatinine-based estimated GFR <90 mL/min/1.73 m2 and 11 (25%) had cystatin C-based estimated GFR <90 mL/min/1.73 m2. After dolutegravir initiation, serum creatinine values significantly increased (+8.6 μmol/L, 95% CI +5.8; +11.4, P < 0.001) and associated estimated GFR significantly decreased (-7.7 mL/min/1.73 m2, 95% CI -10.4; -5.1, P < 0.001). In contrast, there was no significant change in cystatin C value variation and associated estimated GFR. The same results were observed regardless of renal function at baseline.

CONCLUSIONS

Creatinine values increased after dolutegravir initiation, whereas no change was observed for cystatin C values. Use of cystatin C may enable better understanding of plasma creatinine fluctuations after dolutegravir initiation, particularly in high-risk renal patients.

摘要

目的

多替拉韦通过抑制有机阳离子转运体 2 （OCT2）导致血清肌酐升高。血清胱抑素 C 是非 OCT2 依赖性标志物，可能能够在使用多替拉韦时估算肾小球滤过率（GFR）。我们的目标是评估多替拉韦治疗前后基于肌酐和胱抑素 C 的估计肾小球滤过率值的变化。

方法

2016 年 10 月至 2017 年 3 月，在巴黎皮提-萨尔佩特里埃医院，对接受 HIV-1 感染治疗的患者的冷冻血浆样本进行了肌酐和胱抑素 C 的测量，这些患者在开始使用多替拉韦前后接受了测量。使用 CKD-EPI 方程从肌酐和胱抑素 C 值估算平均 GFR。采用配对 t 检验分析变化。

结果

共纳入 44 例患者[中位年龄 48 岁（IQR 36-58），中位 CD4 计数 592 个细胞/mm3（IQR 388-728）]，包括 6 例初治患者和 38 例转换治疗策略的患者[72%患者病毒载量＜50 拷贝/mL，中位 ART 治疗时间 13 年（IQR 5-20）]。在开始使用多替拉韦之前（中位时间 41 天），19 例（43%）患者基于肌酐的估计肾小球滤过率＜90 mL/min/1.73 m2，11 例（25%）患者基于胱抑素 C 的估计肾小球滤过率＜90 mL/min/1.73 m2。多替拉韦治疗后，血清肌酐值显著升高（+8.6 μmol/L，95%CI +5.8；+11.4，P＜0.001），估计肾小球滤过率显著降低（-7.7 mL/min/1.73 m2，95%CI -10.4；-5.1，P＜0.001）。相比之下，胱抑素 C 值变化和相关估计肾小球滤过率没有显著变化。无论基线肾功能如何，都观察到了相同的结果。