Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients

Salisa Wejnaruemarn; Thaninee  Prasoppokakorn; Nattachai  Srisawat; Tongluk Teerasarntipan; Kessarin  Thanapirom; Chonlada  Phathong; Roongruedee Chaiteerakij; Piyawat Komolmit; Pisit Tangkijvanich; Sombat Treeprasertsuk

doi:10.33192/smj.v76i4.268004

Authors

Salisa Wejnaruemarn Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Thaninee Prasoppokakorn Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Nattachai Srisawat Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand / Excellent Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Tongluk Teerasarntipan Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Kessarin Thanapirom Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand / Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
Chonlada Phathong Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Roongruedee Chaiteerakij Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Piyawat Komolmit Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand / Liver Fibrosis and Cirrhosis Research Unit, Chulalongkorn University, Bangkok, Thailand
Pisit Tangkijvanich Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Sombat Treeprasertsuk Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand / Department of Biochemistry and Liver Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

DOI:

https://doi.org/10.33192/smj.v76i4.268004

Keywords:

acute kidney injury, biomarker, cirrhosis, liver-type fatty-acid binding protein, mortality, neutrophil gelatinase-associated lipocalin

Abstract

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients.

Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality.

Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02).

Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality.

References

Piano S, Rosi S, Maresio G, Fasolato S, Cavallin M, Romano A, et al. Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol. 2013;59(3):482-9.

Bucsics T, Krones E. Renal dysfunction in cirrhosis: acute kidney injury and the hepatorenal syndrome. Gastroenterol Rep (Oxf). 2017;5(2):127-37.

Angeli P, Gines P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968-74.

Francoz C, Nadim MK, Durand F. Kidney biomarkers in cirrhosis. J Hepatol. 2016;65(4):809-24.

Siew ED, Ware LB, Ikizler TA. Biological markers of acute kidney injury. J Am Soc Nephrol. 2011;22(5):810-20.

Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008;3(3):665-73.

Arthur JM, Hill EG, Alge JL, Lewis EC, Neely BA, Janech MG, et al. Evaluation of 32 urine biomarkers to predict the progression of acute kidney injury after cardiac surgery. Kidney Int. 2014;85(2):431-8.

Aberg F, Lempinen M, Hollmen M, Nordin A, Makisalo H, Isoniemi H. Neutrophil gelatinase-associated lipocalin associated with irreversibility of pre-liver transplant kidney dysfunction. Clin Transplant. 2014;28(8):869-76.

Doi K, Negishi K, Ishizu T, Katagiri D, Fujita T, Matsubara T, et al. Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit Care Med. 2011;39(11):2464-9.

Siew ED, Ikizler TA, Gebretsadik T, Shintani A, Wickersham N, Bossert F, et al. Elevated urinary IL-18 levels at the time of ICU admission predict adverse clinical outcomes. Clin J Am Soc Nephrol. 2010;5(8):1497-505.

Ferguson MA, Vaidya VS, Waikar SS, Collings FB, Sunderland KE, Gioules CJ, et al. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury. Kidney Int. 2010;77(8):708-14.

Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, Thiessen-Philbrook H, et al. Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology. 2014;60(2):622-32.

Fagundes C, Pepin MN, Guevara M, Barreto R, Casals G, Sola E, et al. Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis. Journal of hepatology. 2012;57(2):267-73.

Xu Y, Xie Y, Shao X, Ni Z, Mou S. L-FABP: A novel biomarker of kidney disease. Clin Chim Acta. 2015;445:85-90.

Ariza X, Graupera I, Coll M, Sola E, Barreto R, Garcia E, et al. Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis. J Hepatol. 2016;65(1):57-65.

Portilla D, Dent C, Sugaya T, Nagothu KK, Kundi I, Moore P, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2008;73(4):465-72.

Treeprasertsuk S, Wongkarnjana A, Jaruvongvanich V, Sallapant S, Tiranathanagul K, Komolmit P, et al. Urine neutrophil gelatinase-associated lipocalin: a diagnostic and prognostic marker for acute kidney injury (AKI) in hospitalized cirrhotic patients with AKI-prone conditions. BMC Gastroenterol. 2015;15:140.

Belcher JM, Garcia-Tsao G, Sanyal AJ, Thiessen-Philbrook H, Peixoto AJ, Perazella MA, et al. Urinary biomarkers and progression of AKI in patients with cirrhosis. Clinical journal of the American Society of Nephrology : CJASN. 2014;9(11):1857-67.

Eguchi A, Hasegawa H, Iwasa M, Tamai Y, Ohata K, Oikawa T, et al. Serum Liver-Type Fatty Acid-Binding Protein Is a Possible Prognostic Factor in Human Chronic Liver Diseases From Chronic Hepatitis to Liver Cirrhosis and Hepatocellular Carcinoma. Hepatol Commun. 2019;3(6):825-37.

Russ KB, Stevens TM, Singal AK. Acute Kidney Injury in Patients with Cirrhosis. J Clin Transl Hepatol. 2015;3(3):195-204.

Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426-37, 37 e1-9.

Jiang QQ, Han MF, Ma K, Chen G, Wan XY, Kilonzo SB, et al. Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis. World J Gastroenterol. 2018;24(21):2300-10.

Asada T, Isshiki R, Hayase N, Sumida M, Inokuchi R, Noiri E, et al. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein. Sci Rep. 2016;6:33077.

Sun J, Guo H, Yu X, Chen J, Zhu H, Qi X, et al. Evaluation of prognostic value of neutrophil-to-lymphocyte ratio in patients with acute-on-chronic liver failure or severe liver injury from chronic HBV infection. Eur J Gastroenterol Hepatol. 2021.