Yukawa Satomi, Watanabe Dai, Uehira Tomoko, Shirasaka Takuma
Department of Advanced Medicine for HIV Infection, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Infectious Diseases, National Hospital Organization Osaka National Hospital, Osaka, Japan.
Department of Advanced Medicine for HIV Infection, Osaka University Graduate School of Medicine, Osaka, Japan; AIDS Medical Center, National Hospital Organization Osaka National Hospital, Osaka, Japan.
J Infect Chemother. 2018 Mar;24(3):199-205. doi: 10.1016/j.jiac.2017.10.015. Epub 2017 Nov 14.
Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys).
PATIENTS & METHODS: HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1). We compared eGFRcre and eGFRcys at the start and after 48 weeks of dolutegravir administration. For the patients providing consent, we measured Cin and Ccr (n = 15, Study 2). We assessed biases and accuracy and compared Cin with eGFRcre, eGFRcys, and Ccr.
There were no differences in serum cystatin C and eGFRcys between baseline and at 48 weeks. Moreover, eGFRcre was significantly less accurate (within 30% of measured GFR) than both eGFRcys and Ccr (40% accuracy compared to 93% and 93%, respectively). eGFRcys was significantly less biased than eGFRcre and Ccr (p < 0.0001, p = 0.00036, respectively). No significant difference between Cin and eGFRcys was observed. eGFRcys was significantly correlated with Cin (γ = 0.85, p < 0.0001).
eGFRcys provided the most precise estimate and most closely approximate Cin in HIV-1-infected Japanese patients with suppressed viremia treated with dolutegravir. We demonstrated clinical benefits of inulin clearance and eGFRcys. This is the first study performing inulin clearance for HIV-1-infected individuals and to show data for eGFRcys from a large cohort following a switch to dolutegravir from other antiretroviral agents.
多替拉韦可能会抑制肾小管中的肌酐转运蛋白并提高血清肌酐水平。我们研究了使用菊粉清除率（Cin）、肌酐清除率（Ccr）以及基于血清肌酐（eGFRcre）和血清胱抑素C（eGFRcys）估算的肾小球滤过率（GFR）的实用性。
纳入了病毒血症得到抑制且抗逆转录病毒药物从其他药物换用多替拉韦的HIV-1感染日本患者（n = 108，研究1）。我们比较了多替拉韦给药开始时和48周后的eGFRcre和eGFRcys。对于提供同意的患者，我们测量了Cin和Ccr（n = 15，研究2）。我们评估了偏差和准确性，并将Cin与eGFRcre、eGFRcys和Ccr进行比较。
基线时和48周时血清胱抑素C和eGFRcys没有差异。此外，eGFRcre的准确性明显低于eGFRcys和Ccr（与测量的GFR相差30%以内）（分别为40%的准确性，而eGFRcys和Ccr分别为93%）。eGFRcys的偏差明显小于eGFRcre和Ccr（分别为p < 0.0001，p = 0.00036）。未观察到Cin和eGFRcys之间有显著差异。eGFRcys与Cin显著相关（γ = 0.85，p < 0.0001）。
在接受多替拉韦治疗且病毒血症得到抑制的HIV-1感染日本患者中，eGFRcys提供了最精确的估算值，并且与Cin最为接近。我们证明了菊粉清除率和eGFRcys的临床益处。这是第一项对HIV-1感染个体进行菊粉清除率测定并展示从其他抗逆转录病毒药物换用多替拉韦后大量队列的eGFRcys数据的研究。
