Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury

Objective: This study is aimed to examine whether urinary L-type fatty acid-binding protein can detect the severity of sepsis with animal sepsis models and septic shock patients complicated with established acute kidney injury. Design: Experimental animal models and a clinical, prospective observational study. Setting: University laboratory and tertiary hospital. Subjects and Patients: One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury. Interventions: Animals were challenged by abdominal (cecal ligation and puncture) and pulmonary (intratracheal lipopolysaccharide injection) sepsis models with different severities that were confirmed by survival analysis (n = 24) and bronchoalveolar lavage fluid analysis (n = 38). Measurements and Main Results: In animal experiments, significant increases of urinary L-type fatty acid-binding protein levels were induced by sepsis (severe cecal ligation and puncture 399.0 +/- 226.8 mu g/g creatinine [n = 12], less-severe cecal ligation and puncture 89.1 +/- 25.3 [n = 11], sham 13.4 +/- 3.4 [n = 10] at 6 hrs, p < .05 vs. sham; 200 mu g of lipopolysaccharide 190.6 +/- 77.4 mu g/g creatinine [n = 6], 50 mu g of lipopolysaccharide 145.4 +/- 32.6 [n = 8], and saline 29.9 +/- 14.9 [n = 5] at 6 hrs, p < .05 vs. saline). Urinary L-type fatty acid-binding protein predicted severity more accurately than blood urea nitrogen, serum creatinine, and urinary N-acetyl-D-glucosaminidase levels. In clinical evaluation, urinary L-type fatty acid-binding protein measured at admission was significantly higher in the nonsurvivors of septic shock with established acute kidney injury than in the survivors (4366 +/- 192 mu g/g creatinine [n = 68] vs. 483 +/- 71 [n = 77], p < .05). Urinary L-type fatty acid-binding protein showed the higher value of area under the receiver operating characteristic curve for mortality compared with Acute Physiology and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) scores (L-type fatty acid-binding protein 0.994 [0.956-0.999], APACHE II 0.927 [0.873-0.959], and SOFA 0.813 [0.733-0.873], p < .05). Conclusions: Our results suggest that urinary L-type fatty acid-binding protein can be a useful biomarker for sepsis complicated with acute kidney injury for detecting its severity. (Crit Care Med 2010; 38: 2037-2042)