Hurry Preete Kapisha, Poulsen Jørgen Hjelm, Bendtsen Flemming, Møller Søren
Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre, Denmark.
Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre, Denmark.
J Gastroenterol Hepatol. 2017 Feb;32(2):473-481. doi: 10.1111/jgh.13492.
Early detection of renal dysfunction in cirrhosis is important, and several renal biomarkers have been put forward. Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are markers of renal dysfunction, but relations to splanchnic and systemic hemodynamics and kinetics are sparsely studied in cirrhosis. In patients with cirrhosis and portal hypertension, we studied plasma levels and renal, hepatic, and peripheral extraction of NGAL and cystatin C and relations to patients characteristics, liver dysfunction, and hemodynamics.
Forty-five cirrhotic patients (Child class A/B/C:15/15/15) and 15 controls were evaluated with a full clinical, biochemical, and hemodynamic assessment. Urine and regional plasma concentrations of NGAL and cystatin C were measured.
There was no significant difference in circulating or hepatic NGAL or cystatin C between all patients and controls but a trend towards increased levels with increasing Child class. In addition, there was a significant renal but no hepatic or systemic extraction of both NGAL and cystatin C (P < 0.001). Plasma NGAL correlated with glomerular filtration rate (r = -0.56, P < 0.0001), and hepatic venous pressure gradient (r = 0.34,P = 0.02) and urinary NGAL correlated with heart rate (r = 0.58, P= 0.007), blood pressure (r = -0.46, P < 0.05), cardiac output (r = 0.45, P < 0.05), and systemic vascular resistance (SVR) (r = -0.48, p < 0.05). Plasma cystatin C correlated with hepatic venous pressure gradient (r = 0.45, P < 0.005), blood pressure (-0.40, P < 0.01), and glomerular filtration rate (r = 0.98, P < 0.000).
Extractions of NGAL and cystatin C levels seem largely unaffected by the severity of liver disease in cirrhosis with a renal extraction. These biomarkers therefore have the potential of being both valuable in diagnosing renal failure and reflecting the degree of portal hypertension and systemic haemodynamic changes.
肝硬化患者肾功能障碍的早期检测至关重要，目前已提出多种肾脏生物标志物。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和胱抑素C是肾功能障碍的标志物，但在肝硬化患者中，它们与内脏和全身血流动力学及动力学的关系鲜少被研究。在肝硬化和门静脉高压患者中，我们研究了NGAL和胱抑素C的血浆水平、肾脏、肝脏及外周摄取情况，以及它们与患者特征、肝功能障碍和血流动力学的关系。
对45例肝硬化患者（Child分级A/B/C：15/15/15）和15例对照者进行了全面的临床、生化和血流动力学评估。测定了尿液和局部血浆中NGAL和胱抑素C的浓度。
所有患者与对照者之间循环或肝脏中的NGAL或胱抑素C水平无显著差异，但随着Child分级增加有升高趋势。此外，NGAL和胱抑素C均有显著的肾脏摄取，但无肝脏或全身摄取（P <0.001）。血浆NGAL与肾小球滤过率（r = -0.56，P <0.0001）及肝静脉压力梯度（r =0.34，P =0.02）相关，尿NGAL与心率（r =0.58，P =0.007）、血压（r = -0.46，P <0.05）、心输出量（r =0.45，P <0.05）及全身血管阻力（SVR）（r = -0.48，P <0.05）相关。血浆胱抑素C与肝静脉压力梯度（r =0.45，P <0.005）、血压（-0.40，P <0.01）及肾小球滤过率（r =0.98，P <0.000）相关。
在有肾脏摄取的肝硬化患者中，NGAL和胱抑素C水平的摄取似乎在很大程度上不受肝脏疾病严重程度的影响。因此，这些生物标志物在诊断肾衰竭以及反映门静脉高压程度和全身血流动力学变化方面均具有潜在价值。
