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.


METHODS
Experimental animal models and a clinical, prospective observational study.


METHODS
University laboratory and tertiary hospital.


METHODS
One hundred fourteen human L-type fatty acid-binding protein transgenic mice and 145 septic shock patients with established acute kidney injury.


METHODS
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).


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 μg/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 μg of lipopolysaccharide 190.6 ± 77.4 μg/g creatinine [n = 6], 50 μg 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 μg/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.
Doi
Kent
K
Department of Nephrology and Endocrinology, Japan Science and Technology Agency/Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development, the University of Tokyo, Tokyo, Japan.
Noiri
Eisei
E
Maeda-Mamiya
Rui
R
Ishii
Tomoko
T
Negishi
Kousuke
K
Hamasaki
Yoshifumi
Y
Fujita
Toshiro
T
Yahagi
Naoki
N
Koide
Hikaru
H
Sugaya
Takeshi
T
Nakamura
Tsukasa
T
D058186:Acute Kidney Injury / Q000150:complications* / Q000175:diagnosis / Q000652:urine; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications* / Q000175:diagnosis / Q000652:urine
D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins