Infectious Diseases Department, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France.
Pierre Louis Institute of Epidemiology and Public Health (IPLESP, UMRS 1136), Paris, France.
J Antimicrob Chemother. 2018 Jul 1;73(7):1935-1939. doi: 10.1093/jac/dky112.
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.
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.
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.
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.
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。
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。
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。
多替拉韦治疗后肌酐值升高，而胱抑素 C 值无变化。使用胱抑素 C 可能能够更好地理解多替拉韦治疗后血浆肌酐的波动，特别是在高风险肾功能不全患者中。
