Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.

AIM: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases. METHODS: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.25 or 0.5 mg/kg/min calf thymus histones for 240 min from caudal vena cava. RESULTS: After the administration of histone, urinary L-FABP and gene expression of an oxidative stress marker in the kidney increased in a histone dose-dependent manner before increased serum creatinine. Upon further investigation, fibrin deposition in the glomerulus was observed and it tended to be remarkable in the high dose administrated groups. The levels of coagulation factor were significantly changed after the administration of histone, and these were significantly correlated with the levels of urinary L-FABP. CONCLUSIONS: Firstly, it was suggested that histone is one of the causative agents for the urinary L-FABP increase at an early stage of the disease with a risk of acute kidney injury. Secondly, urinary L-FABP could be a marker reflecting the changes of coagulation system and microthrombus caused by histone in the early stage of acute kidney injury before becoming severely ill and maybe a guide to early treatment initiation.

First Experience Addressing the Prognostic Utility of Novel Urinary Biomarkers in Patients With COVID-19.

Urine 11-dehydro-thromboxane B2 (u11-dh-TxB2), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and liver-type fatty acid binding protein levels (L-FABP) at the time of hospitalization were higher in coronavirus disease 2019 (COVID-19) patients with adverse events vs without events. Higher u11-dh-TxB2 and L-FABP levels were associated with longer hospitalization, more thrombotic events, and greater mortality, providing evidence for potential utility as early prognostic biomarkers for COVID-19.

Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers.

SUBJECTS: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary ß2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low ß2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were ß2-microglobulin; severe versus moderate + mild: 2,457 µg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 µg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary ß2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend. CONCLUSIONS: Evaluating urinary biomarkers such as ß2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.