Fatty acid binding proteins (FABPs) – a new laboratory biomarker for kidney diseases
Keywords:fatty acid binding protein (FABP), biomarker, kidney diseases
Fatty acid binding proteins (FABPs) are a family of intracellular proteins involved in metabolism of lipids. By regulating the intracellular level of free fatty acids, those proteins indirectly influence intracellular signaling pathways. FABPs also play a role in regulation of cell growth and differentiation, and exert a significant antioxidant effect. Some reports suggest that FABPs are released by various organs (heart, liver, intestines, kidneys) in response to tissue damage. The article briefly summarizes the structure, classification and function of FABPs and discusses the applicability of liver- (L-FABP) and heart-type (H-FABP) FABPs in laboratory diagnosis of selected clinical entities, particularly kidney diseases.
Kaikaus RM, Bass NM, Ockner RK. Functions of fatty acid binding proteins. Experientia. 1990;46:617–630.
Chmurzyńska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006;47(1):39–48.
Plasma lipids and lipoproteins. In: Crook MA. Clinical Biochemistry and Metabolic Medicine. 8 th ed. UK, London, Hodder & Stoughton; 2012. p. 201–216.
Mishkin S, Stein L, Gatmaitan Z, Arias IM. The binding of fatty acids to cytoplasmic proteins: binding to Z-protein in liver and other tissues of the rat. Biochem Biophys Res Commun. 1972;47(5):997–1003.
Ockner RK, Manning JA, Poppenhausen RB, Ho WKL. A binding protein for fatty acids in cytosol of intestinal mucosa, liver, myocardium and other tissues. Science. 1972;177(4043):56–58.
Zimmerman AW, Veerkamp JH. New insights into the structure and function of fatty acid-binding proteins. Cell Mol Life Sci. 2002;59(7):1096–1116.
Hanhoff T, Lucke C, Spener F. Insights into binding of fatty acids by fatty acids binding proteins. Molecular and Cellular Biochemistry. 2002;239(1–2):45–54.
Storch J, Thumser AEA. The fatty acid transport function of fatty acid-binding proteins. Biochimica et Bioiphysica Acta. 2000;1486(1):28–44.
Storch J, McDermott L. Structural and functional analysis of fatty acid-binding proteins. J Lipid Res. 2009;50(Suppl.):S126-S131.
Wang GQ, Bonkovsky HL, de Lemos A, Burczynski FJ. Recent insights into the biological functions of liver fatty acid binding protein 1. J Lipid Res. 2015;56(12):2238–2247.
Kleine AH, Glatz JFC, Van Nieuwenhoven FA, Van der Vusse GJ. Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man. Mol Cell Biochem. 1992;116(1–2):155–162.
Glatz JFC, Kleine AH, Van Nieuwenhoven FA, Hermens WT, Van Dieijen-Visser MP, Van der Vusse GJ. Fatty acid-binding protein as a plasma marker for the estiamation of myocardial infarct size in humans. Br Heart J. 1994;71(2):135–140.
Haastrup B, Gill S, Kristensen SR, Jorgensen PJ, Glatz JFC, Haghfelt T et al. Biochemical marker of ischaemia for the early identification of acute myocardial infarction without ST-segment elevation. Cardiology. 2000;94(4):254–261.
Pelsers MMAL, Hermens WT, Glatz JFC. Fatty acid-binding proteins as plasma markers of tissue injury. Clinica Chimica Acta. 2005;352(1–2):15–35.
Ghani F, Wu AHB, Graff L, Petry C, Armstrong G, Prigent F et al. Role of heart-type fatty acid-binding protein in early detection of acute myocardial infarction. Clin Chem. 2000;46(5):718–719.
Kanda T, Fujii H, Tani T, Murakami H, Suda T, Sakai Y et al. Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology. 1996;110(2):339–343.
Lieberman JM, Marks WH, Cohn S, Jaicks R, Woode L, Sacchettini J, et al. Organ failure, infection and the systemic inflammatory response syndrome are associated with elevated levels of urinary intestinal fatty acid binding protein: study of 100 consecutive patients in a surgical intensive care unit. J Trauma. 1998;45(5):900–906.
Holmes IV JH, Lieberman JM, Probert CB, Marks WH, Hill ME, Paull DL, et al. Elevated intestinal fatty acid-binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis. J Surg Res. 2001;100(2):192–196.
Kaufmann SS, Lyden ER, Marks WH, Lieberman J, Sudan DL, Fox IF, et al. Lack of utility of intestinal fatty acid-binding protein levels in predicting intestinal allograft rejection. Transplantation 2001;71(8):1058–1060.
Maezawa H, Inagaki T, Okano K. A low molecular weight binding protein for organic anions (Z protein) from human hepatic cytosol: purification and quantitation. Hepatology. 1981;1(3):221–227.
Maatman RGHJ, Van Kuppevelt THMSM, Veerkamp JH. Two types of fatty acid-binding protein in human kidney. Biochem J. 1991;273(Pt 3):759–766.
Maatman RGHJ, Van De Westerlo EMA, Van Kuppevelt THMSM, Veerkamp JH. Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Biochem J. 1992;288(Pt 1):285–290.
Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clin Chim Acta. 2006;374(1–2):1–7.
Arici M, Brown J, Williams M, Harris KPG, Walls J, Brunskill NJ. Fatty acids carried on albumin modulate proximal tubular cell fibronectin production: a role for protein kinase C. Nephrol Dial Transplant. 2002;17(10):1751–1757.
Arici M, Chana R, Lewington A, Brown J, Brunskill NJ. Stimulation of proximal tubular cell apoptosis by albumin-bound fatty acids mediated by peroxisome proliferator activated receptor-gamma. J Am Soc Nephrol. 2003;14(1):17–27.
Kamijo A, Kimura K, Sugaya T, Yamanouchi M, Hase H, Kaneko T, et al. Urinary free fatty acids bound to albumin aggravate tubulointerstitial damage. Kidney Int. 2002;62(5):1628–1637.
Thomas ME, Harris KP, Walls J, Furness PN, Brunskill NJ. Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria. Am J Physiol Renal Physiol. 2002(4);283:F640–F647.
Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol. 2012;2(2):1303–1353.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, Acute Dialysis Quality Initiative workgroup. Acute Dialysis Quality Initiative workgroup: Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI). Crit Care. 2004;8(4):R204– R212.
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Dialysis Quality Injury Network. Acute Kidney Injury Network: Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.
Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2(1):S1–S141.
Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:63–493.
Sirota JC, Klawitter J, Edelstein CL. Biomarkers of acute kidney injury. Hindawi Publishing Corporation, Journal of Toxicology. 2011;article ID 328120,10 pages.
de Geus HRH, Betjes MG, Bakker J. Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Clin Kidney J. 2012;5(2):102–108.
Alge JL, Arthur JM. Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. Clin J Am Soc Nephrol. 2015;10(1):147–155.
Król E, Rutkowski B. Przewlekła choroba nerek – klasyfikacja, epidemiologia i diagnostyka. Forum Nefrol. 2008;1(1):1–6.
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Clinical Practice Guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl. 1):S1–S266.
Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67(6):2089–2100.
Kidney Disease: Improving Global Outcomes. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3(1):S1–S163.
Hu MC, Kuro-o M, Moe OW. The emerging role of Klotho in clinical nephrology. Nephrol Dial Transplant. 2012;27(7):2650–2657.
Wolf M. Update on fibroblast growth factor 23 in chronic kidney disease. Kidney Int. 2012;82(7):737–747.
Olauson H, Larsson TE. FGF23 and Klotho in chronic kidney disease. Curr Opin Nephrol Hypertens. 2013;22(4):397–404.
Wong MG, Pollock CA. Biomarkers in kidney fibrosis: are they useful? Kidney Int Suppl. 2014;4(1):79–83.
Nickolas TL, Barasch J, Devarajan P. Biomarkers in acute and chronic kidney disease. Curr Opin Nephrol Hypertens. 2008;17(2):127–132.
Devarajan P. The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis. 2010;17(6):469–479.
Kawai A, Kusaka M, Kitagawa F, Ishii J, Fukami N, Maruyama T, et al. Serum liver-type fatty acid-binding protein predicts recovery of graft function after kidney transplantation from donors after cardiac death. Clin Transplant. 2014;28(6):749–754.
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):465–472.
Matsui K, Kamijo-Ikemori A, Sugaya T, Yasuda T, Kimura K. Usefulness of urinary biomarkers in early detection of acute kidney injury after cardiac surgery in adults. Circ J. 2012;76(1):213–220.
Nakamura T, Sugaya T, Node K, Ueda Y, Koide H. Urinary excretion of liver type fatty acid-binding protein in contrast medium-induced nephropathy. Am J Kidney Dis. 2006;47(3):439–444.
Manabe K, Kamihata H, Motohiro M, Senoo T, Yoshida S, Iwasaka T. Urinary liver-type fatty acid-binding protein level as a predictive biomarker of contrast-induced acute kidney injury. Eur J Clin Invest. 2012;42(5):557–563.
Negishi K, Noiri E, Sugaya T, Li S, Megyesi J, Nagothu K, et al. A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure. Kidney Int. 2007;72(3):348–358.
Nakamura T, Sugaya T, Koide H. Urinary liver-type fatty acid-binding protein in septic shock: effect of polymyxin B-immobilized fiber hemoperfusion. Shock. 2009;31(5):454–459.
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):708–714.
Kamijo A, Sugaya T, Hikawa A, Yamanouchi M, Hirata Y, Ishimitsu T, et al. Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: a multicenter trial. J Lab Clin Med. 2005;145(3):125–133.
Kamijo A, Kimura K, Sugaya T, Hikawa A, Yamanouchi M, Hikawa A et al. Urinary fatty acid-binding protein as a new clinical marker of the progression of chronić renal disease. J Lab Clin Med. 2004;143(1):23–30.
Panduru NM, Forsblom C, Saraheimo M, Thorn L, Bierhaus A, Humpert PM, et al. Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care. 2013;36(7):2077–2083.
Kamijo-Ikemori A, Sugaya T, Ichikawa D, Hoshino S, Matsui K, Yokoyama T, et al. Urinary liver type fatty acid binding protein in diabetic nephropathy. Clin Chim Acta. 2013;424:104–108.
Mou S, Wang Q, Li J, Shi B, Ni Z. Urinary excretion of liver-type fatty acid-binding protein as a marker of progressive kidney function deterioration in patients with chronic glomerulonephritis. Clin Chim Acta. 2012;413(1–2):187–191.
Kamijo-Ikemori A, Sugaya T, Obama A, Hiroi J, Miura H, Watamabe M, et al. Liver-type fatty acid-binding protein attenuates renal injury induced by unilateral ureteral obstruction. Am J Pathol. 2006;169(4):1107–1117.
Parmaksiz G, Noyan A, Dursun H, Ince E, Anarat R, Cengiz N. Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1 and L-FABP. Pediatr Nephrol. 2016;31(1):97–103.
Tanaka T, Noiri E, Yamamoto T, Sugaya T, Negishi K, Maeda R, et al. Urinary human L-FABP is a potential biomarker to predict COX-inhibitor-induced renal injury. Nephron Exp Nephrol. 2008;108(1):e19-e26.
How to Cite
Copyright (c) 2017 Łukasz Dobrek
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.