Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Atherosclerosis. 2013 Apr;227(2):408-13. doi: 10.1016/j.atherosclerosis.2013.01.009. Epub 2013 Jan 18.
Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.
This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.
U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.
This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.
中性粒细胞明胶酶相关脂质运载蛋白(NGAL)表明肾小管肾损伤、中性粒细胞激活和可能的动脉粥样硬化形成,但社区中尿 NGAL(u-NGAL)与心血管死亡的前瞻性关联尚不清楚。
本研究评估了瑞典 597 名 78 岁男性人群中尿和血清 NGAL 与死亡率之间的关系。在研究期间(中位随访 8.1 年),261 名男性死亡,90 名死于心血管原因。
在 Cox 回归模型中,u-NGAL 与全因和心血管死亡率增加相关(四分位 4 与四分位 1 相比,HR 2.0,95%CI 1.0-4.0,P<0.05),独立于心血管危险因素、CRP 和胱抑素 C 估计肾小球滤过率(eGFRCysC),但不依赖于尿白蛋白(u-Alb)。低 eGFRCysC(≤60 mL/min)、高 u-Alb(≥3 mg/mmol Cr)和高 u-NGAL(≥1.19 μg/mmol Cr)的组合与心血管死亡率增加 9 倍(P<0.001)和全因死亡率增加 3 倍(P<0.001)相关。血清 NGAL 与全因死亡风险增加相关,独立于其他心血管危险因素(四分位 4 与 1 相比,HR 1.4,95%CI 1.0-1.9,P<0.05),但与 CRP、eGFRCysC 或 u-Alb 调整后无关。
本社区研究首次表明,肾小管肾生物标志物 u-NGAL 与心血管和全因死亡率增加相关,独立于心血管危险因素和肾小球滤过。需要进一步研究来评估 NGAL 在临床实践中的应用。