Increased urinary excretion of bilirubin oxidative metabolites in septic patients: a new marker for ocidative stress in vivo

背景。胆红素氧化代谢物（BOMs）是由胆红素产生的，因为它具有清除自由基的作用。在脓毒症期间，过量的自由基产生，它们在病理生理过程中起重要作用。我们研究了人类在脓毒症条件下尿中BOM的排泄量是否会增加，并将BOM水平与其他已知的炎症临床参数进行了比较。采用酶联免疫吸附法测定19例脓毒症患者和28例非脓毒症对照患者尿液中BOM的浓度，并结合抗胆红素抗体。脓毒症患者尿BOM水平明显高于对照组（21.6±2.5 vs . 1.4±0.4 mol/g肌酐，P < 0.001）。虽然尿BOM与血清总胆红素水平呈线性相关（r = 0.392, P = 0.008），但脓毒症组血清胆红素水平并未显著高于对照组（P = 0.072）。BOM水平与体温（r = 0.801, P < 0.001）、外周血白细胞计数（r = 0.590, P < 0.001）、血清c反应蛋白（r = 0.653, P < 0.001）、急性生理和慢性健康评估（APACHE II）评分（r = 0.467, P = 0.003）相关。这些结果表明，脓毒症患者尿中BOMs增加。这种增加表明尿BOM水平是一个可能的标志物，持续监测脓毒症的严重程度在临床实践中。

Background. Bilirubin oxidative metabolites (BOMs) are generated from bilirubin as a result of its scavenging action against free radicals. During sepsis, excess amounts of free radicals are produced, and they play an important role in the pathophysiological process. We studied whether urinary excretion of BOMs would increase under septic conditions in humans and compared BOM levels with other well-established clinical parameters of inflammation.Methods. In 19 septic patients and 28 nonseptic control patients, the BOM concentrations in urine were measured by enzyme-linked immunosorbent assay with an anti-bilirubin antibody.Results. Urinary BOM levels in septic patients were much higher than those in control patients (21.6±2.5 v.s. 1.4±0.4 mol/g creatinine, P < 0.001). Although there was a linear correlation between urinary BOM and serum total bilirubin levels (r = 0.392, P = 0.008), serum bilirubin levels were not significantly higher in the septic group than in the control group (P = 0.072). BOM levels correlated with body temperature (r = 0.801, P < 0.001), white blood cell counts in the peripheral blood (r = 0.590, P < 0.001), serum C-reactive protein (r = 0.653, P < 0.001), and the acute physiological and chronic health evaluation (APACHE II) score (r = 0.467, P = 0.003).Conclusions. These results demonstrated a urinary increase in BOMs in septic patients. This increase indicates that urinary BOM level is a possible marker for continuous monitoring of sepsis severity in clinical practice.