Schilder Louise, Nurmohamed S Azam, ter Wee Pieter M, Paauw Nanne J, Girbes Armand R J, Beishuizen Albertus, Beelen Robert H J, Groeneveld A B Johan
Crit Care. 2014 Apr 22;18(2):R78. doi: 10.1186/cc13838.
Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.
Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).
Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).
The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.
中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是急性肾损伤(AKI)的生物标志物,其水平反映了重症患者的疾病严重程度。然而,连续性静脉-静脉血液滤过(CVVH)可能会通过清除滤器中活化中性粒细胞释放的NGAL或使其释放而影响血浆水平,这取决于所应用的抗凝方案。因此,我们研究了AKI患者中CVVH对NGAL的处理情况。
在开始CVVH之前立即采集滤器前血液。在CVVH进行10、60、180和720分钟后,从滤器前和滤器后(进、出口)血液及超滤液中采集样本。研究了采用以下抗凝方案的CVVH:高出血倾向患者不抗凝(n = 13)、普通肝素(n = 8)或枸橼酸钠(n = 21)。采用酶联免疫吸附测定(ELISA)法测定NGAL水平。
进、出口处NGAL浓度相似,且在任何抗凝组中浓度均未随时间变化;因此未发生NGAL的净清除或产生。滤器入口处NGAL浓度与CVVH开始时及CVVH运行结束时的疾病严重程度相关。基于枸橼酸盐的CVVH超滤液中NGAL浓度较低(P = 0.03),且随时间降低,与所给予的抗凝剂无关(P < 0.001)。NGAL的筛系数和清除率较低且随时间降低(P < 0.001)。
AKI重症患者中NGAL的血浆水平和生物标志物价值不受CVVH影响,因为滤器清除率较低。此外,无论采用何种抗凝方法,均无证据表明中性粒细胞在滤器内释放NGAL。