Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center, San Francisco, California.
Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Clin J Am Soc Nephrol. 2018 Sep 7;13(9):1321-1329. doi: 10.2215/CJN.01700218. Epub 2018 Aug 28.
Tenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, -1-microglobulin, -2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase-associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR.
Median eGFR before tenofovir initiation was 103 (interquartile range, 88-116) ml/min per 1.73 m. During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m and was stable afterward (decrease of 0.62; 95% confidence interval, -0.85 to 2.1 ml/min per 1.73 m per year). After multivariable adjustment, higher baseline -2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines.
Urinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_28_CJASNPodcast_18_9_S.mp3.
富马酸替诺福韦二吡呋酯（替诺福韦）与 HIV 感染者的肾脏损伤和功能障碍的生物标志物浓度升高有关。这些肾脏生物标志物与纵向肾功能下降的关系尚不清楚。
设计、地点、参与者和测量：我们评估了 198 名男性和女性 HIV 患者在 2009 年至 2015 年期间开始使用替诺福韦后，14 种尿液肾脏损伤生物标志物与 eGFR 变化之间的相关性。尿液生物标志物包括白蛋白/肌酐比、-1 微球蛋白、-2 微球蛋白、胱抑素 C、肾损伤分子 1（KIM-1）、IL-18、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、簇蛋白、骨桥蛋白、尿调蛋白、单核细胞趋化蛋白 1、EGF、三叶因子 3 和几丁质酶 3 样蛋白 1。我们使用多变量线性混合效应模型，控制人口统计学、传统肾脏疾病危险因素和 HIV 相关危险因素，以评估基线生物标志物与 eGFR 第一年变化之间的相关性，以及第 1 年和第 1 年生物标志物变化与第 1 年至第 3 年 eGFR 变化之间的相关性。我们使用最小绝对收缩和选择算子方法来确定与 eGFR 变化联合相关的一组简化生物标志物。
替诺福韦起始前 eGFR 中位数为 103（四分位距，88-116）ml/min/1.73m。在替诺福韦使用的第一年，eGFR 平均下降 9.2（95%置信区间，6.5 至 11.9）ml/min/1.73m，此后保持稳定（每年下降 0.62；95%置信区间，-0.85 至 2.1 ml/min/1.73m）。在多变量调整后，较高的基线 -2 微球蛋白、KIM-1 和簇蛋白与第一年 eGFR 下降幅度较大相关，而较高的基线尿调蛋白与 eGFR 下降幅度较小相关。第 1 年尿胱抑素 C 升高和第 1 年 IL-18 升高与第 1 年至第 3 年 eGFR 每年下降幅度较大相关。简化模型确定了较高的预替诺福韦簇蛋白和 KIM-1、较低的预替诺福韦尿调蛋白和较高的第 1 年 IL-18 与更大的 eGFR 下降相关。
在开始使用替诺福韦之前和之后测量的肾脏损伤生物标志物与 HIV 患者随后的 eGFR 变化有关。
