Jotwani Vasantha, Scherzer Rebecca, Abraham Alison, Estrella Michelle M, Bennett Michael, Devarajan Prasad, Anastos Kathryn, Cohen Mardge H, Nowicki Marek, Sharma Anjali, Young Mary, Tien Phyllis C, Grunfeld Carl, Parikh Chirag R, Shlipak Michael G
Department of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA.
Antivir Ther. 2014;19(1):79-87. doi: 10.3851/IMP2677. Epub 2013 Aug 23.
In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1), are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.
In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1 and albumin-to-creatinine ratio (ACR) in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women's Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.
After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (P<0.0001), 12% for KIM-1 (P=0.081) and 47% for ACR (P<0.0001). Higher HIV RNA level (15% per 10-fold increase; P<0.0001), lower CD4(+) lymphocyte count (8% per doubling; P=0.0025), HCV infection (30%; P=0.00018) and lower high-density lipoprotein (5% per 10 mg/dl; P=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%; P<0.0001) and diabetes (47%; P=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase; P=0.0004) was also associated with higher ACR.
HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.
在感染HIV的女性中，新型肾小管间质损伤标志物白细胞介素-18（IL-18）和肾损伤分子-1（KIM-1）的尿液浓度与肾功能下降及全因死亡率相关。我们推测，与未感染的对照组相比，具有保留的肾脏滤过功能的HIV感染者会有更广泛的肾损伤，这可通过尿液损伤标志物来确定，并且肾小管间质损伤的危险因素与蛋白尿的危险因素不同。
在这项横断面研究中，我们比较了参与女性机构间HIV研究的908名感染HIV的女性和289名未感染HIV的女性的IL-18、KIM-1尿液浓度以及白蛋白与肌酐比值（ACR），利用了1999年至2000年访视期间储存的尿液标本。
经过多变量调整的线性回归分析后，感染HIV的个体中，IL-18的平均尿液浓度高38%（P<0.0001），KIM-1高12%（P=0.081），ACR高47%（P<0.0001）。更高的HIV RNA水平（每增加10倍升高15%；P<0.0001）、更低的CD4(+)淋巴细胞计数（每翻倍降低8%；P=0.0025）、丙型肝炎病毒（HCV）感染（30%；P=0.00018）以及更低的高密度脂蛋白（每10mg/dl降低5%；P=0.0024）均与更高的IL-18浓度相关。相比之下，高血压（81%；P<0.0001）和糖尿病（47%；P=0.018）是ACR升高的最强预测因素之一，尽管HIV RNA水平（每增加10倍升高15%；P=0.0004）也与ACR升高相关。
感染HIV的女性比未感染的女性有更广泛的肾小管间质和肾小球损伤，但相关因素在尿液生物标志物中有所不同。应研究尿液生物标志物的组合，以进一步明确感染HIV女性的早期肾损伤特征。
