Peralta Ca, Scherzer R, Grunfeld C, Abraham A, Tien Pc, Devarajan P, Bennett M, Butch Aw, Anastos K, Cohen Mh, Nowicki M, Sharma A, Young Ma, Sarnak Mj, Parikh Cr, Shlipak Mg
Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA.
HIV Med. 2014 May;15(5):291-300. doi: 10.1111/hiv.12113. Epub 2013 Dec 3.
Chronic kidney disease (CKD) is common in HIV-infected individuals, and is associated with mortality in both the HIV-infected and general populations. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
We evaluated the associations of urinary interleukin-18 (IL-18), liver fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and the albumin-to-creatinine ratio (ACR) with 10-year, all-cause death in 908 HIV-infected women. Serum cystatin C was used to estimate the glomerular filtration rate (eGFRcys).
There were 201 deaths during 9269 person-years of follow-up. After demographic adjustment, compared with the lowest tertile, the highest tertiles of IL-18 [hazard ratio (HR) 2.54; 95% confidence interval (CI) 1.75-3.68], KIM-1 (HR 2.04; 95% CI 1.44-2.89), NGAL (HR 1.50; 95% CI 1.05-2.14) and ACR (HR 1.63; 95% CI 1.13-2.36) were associated with higher mortality. After multivariable adjustment including adjustment for eGFRcys, only the highest tertiles of IL-18 (HR 1.88; 95% CI 1.29-2.74) and ACR (HR 1.46; 95% CI 1.01-2.12) remained independently associated with mortality. Findings for KIM-1 were borderline (HR 1.41; 95% CI 0.99-2.02). We found a J-shaped association between L-FABP and mortality. Compared with persons in the lowest tertile, the HR for the middle tertile of L-FABP was 0.67 (95% CI 0.46-0.98) after adjustment. Associations were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools with which to identify early kidney injury in persons with HIV infection.
慢性肾脏病（CKD）在HIV感染个体中很常见，并且与HIV感染人群和普通人群的死亡率相关。肾小管损伤的尿液标志物与未来患肾脏疾病的风险相关，但与死亡率的关联尚不清楚。
我们评估了908名HIV感染女性的尿白细胞介素-18（IL-18）、肝脏脂肪酸结合蛋白（L-FABP）、肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）以及白蛋白与肌酐比值（ACR）与10年全因死亡的关联。血清胱抑素C用于估算肾小球滤过率（eGFRcys）。
在9269人年的随访期间有201例死亡。经人口统计学调整后，与最低三分位数相比，IL-18的最高三分位数[风险比（HR）2.54；95%置信区间（CI）1.75 - 3.68]、KIM-1（HR 2.04；95%CI 1.44 - 2.89）、NGAL（HR 1.50；95%CI 1.05 - 2.14）和ACR（HR 1.63；95%CI 1.13 - 2.36）与更高的死亡率相关。在包括eGFRcys调整在内的多变量调整后，只有IL-18的最高三分位数（HR 1.88；95%CI 1.29 - 2.74）和ACR（HR 1.46；95%CI 1.01 - 2.12）仍与死亡率独立相关。KIM-1的结果处于临界值（HR 1.41；95%CI 0.99 - 2.02）。我们发现L-FABP与死亡率之间呈J形关联。调整后，与最低三分位数的人相比，L-FABP中间三分位数的HR为0.67（95%CI 0.46 - 0.98）。当IL-18、ACR和L-FABP同时纳入模型时，关联更强。
在HIV感染女性中，一些肾小管损伤的尿液标志物与死亡风险相关，独立于eGFRcys和ACR。这些标志物是识别HIV感染患者早期肾损伤的潜在工具。
