Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 7, July, p. 955–962
Publication type: original article
L-FABP and IL-6 as markers of chronic kidney damage in children after hemolytic uremic syndrome
1 Department of Pediatric Nephrology with Dialysis Division for Children, Zabrze, Poland
2 Department and Clinic of Pediatrics, SMDZ in Zabrze, SUM in Katowice, Poland
3 Chair and Department of Medical and Molecular Biology, SMDZ in Zabrze, SUM in Katowice, Poland
Background. Hemolytic-uremic syndrome (HUS) is a form of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). From a clinical point of view, it is important to search for markers that allow for early identification of patients at risk of a poor prognosis.
Objectives. The study evaluated the serum and urine levels of liver-type fatty acid binding protein (L-FABP) and interleukin 6 (IL-6).
Material and Methods. The study was conducted in 29 children with a history of HUS. The relationship between L-FABP and IL-6 and anthropometric measurements, the value of estimated glomerular filtration rate (eGFR) and albuminuria were additionally evaluated.
Results. In children after HUS, L-FABP and IL-6 concentration in both serum and urine was significantly higher in comparison to the control group. No differences in L-FABP and IL-6 concentration in serum and urine depending on the type of HUS and gender were noted. Correlation between L-FABP and IL-6 in serum and urine with eGFR and urine albumin-creatinine ratio (ACR) in the total group of patients after HUS was not detected. In the group of children after 6 month observation after HUS, a negative correlation of L-FABP concentration with eGFR was found.
Conclusion. The results indicate that the higher concentration of L-FABP in serum and urine of children with a history of HUS can be the result of protracted injury initiated during the acute phase of the disease. Lack of correlation of L-FABP concentration with the ACR may be associated with a short (less than 6 months) observation after acute renal failure or merely temporary renal tubular damage in the acute phase of the disease. In contrast, higher levels of IL-6 in serum and urine in children after HUS compared to healthy children and the negative correlation of L-FABP concentration and eGFR in children after 6 month observation after HUS may confirm their participation in CKD. Thus, L-FABP and IL-6 seem to be good biomarkers of chronic kidney damage in survivors of the acute phase of HUS.
children, interleukin 6, chronic kidney disease, hemolytic-uremic syndrome, liver-type fatty acid binding protein
- Adamczuk D, Bieroza I, Roszkowska-Blaim M. Zespół hemolityczno-mocznicowy. Nowa Pediatr. 2009;2:63–67.
- Franchini M. Atypical hemolytic uremic syndrome: From diagnosis to treatment. Clin Chem Lab Med. 2015;53:1679–1688.
- Żurowska A. Zespół hemolityczno-mocznicowy u dzieci i młodzieży. Forum Nefrol. 2012;5:283–288.
- Jander A, Krakowska A, Tkaczyk M. Atypowy zespół hemolityczno-mocznicowy – opis przypadku. Med Og Nauk Zdr. 2013;19:75–77.
- Nester CM, Barbour T, de Cordoba SR, et al. Atypical aHUS: State of the art. Mol Immunol. 2015;67:31–42.
- Picard C, Burtey S, Bornet C, Curti C, Montana M, Vanelle P. Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome. Pathol Biol. 2015;63:136–143.
- Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15–39.
- Wong E, Challis R, Sheerin N, Johnson S, Kavanagh D, Goodship TH. Patient stratification and therapy in atypical haemolytic uraemic syndrome (aHUS). Immunobiology. 2016;221:715–718.
- Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.
- Lumbreras Fernández J, Cruz Rojo J, Iñigo Martín G, Muley Alonso R, Vara Martín J. Hemolytic uremic syndrome: Long term renal injury. Ann Pediatr. 2010;72:309–316.
- Choromańska B, Myśliwiec P, Dadan J, Hady HR, Chabowski A. Znaczenie kliniczne białek wiążących kwasy tłuszczowe (FABPs). Postepy Hig Med Dosw. 2011;65:759–763.
- Yamamoto T, Noiri E, Ono Y, et al. Renal L-type fatty acid binding protein in acute ischemic injury. J Am Soc Nephrol. 2007;18:2894–2902.
- Kalinowska A, Harasim E, Łukaszuk B, Chabowski A. Białka transportujące kwasy tłuszczowe a metabolizm lipidów w mięśniu sercowym. Czyn Ryz. 2009;4:43–49.
- Funaoka H, Kanda T, Fujii H. Intestinal fatty acid-binding protein (I-FABP) as a new biomarker for intestinal diseases. Rinsho Byori. 2010; 58:162–168.
- 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.
- Kamijo-Ikemori A, Sugaya T, Matsui K, Yokoyama T, Kimura K. Roles of human liver type fatty acid binding protein in kidney disease clarified using hL-FABP chromosomal transgenic mice. Nephrol (Carlton). 2011;16:539–544.
- Łukaszewicz M, Mroczko B, Szmitkowski M. Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease. Pol Arch Med Wewn. 2007;117:247–251.
- Moore E, Bellomo R, Nichol A. Biomarkers of acute kidney injury in anesthesia, intensive care and major surgery: From the bench to clinical research to clinical practice. Minerva Anestesiol. 2010;76: 425–440.
- Kokot M, Biolik G, Ziaja D, et al. Assessment of subclinical acute kidney injury after abdominal aortic aneurysm surgery using novel markers L-FABP and H-FABP. Nefrologia. 2014;34:628–636.
- Pajek J, Škoberne A, Šosterič K, et al. Non-inferiority of creatinine excretion rate to urinary L-FABP and NGAL as predictors of early renal allograft function. BMC Nephrol. 2014;15:117.
- Parr SK, Clark AJ, Bian A, et al. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury. Kidney Int. 2015;87:640–648.
- Culig Z, Steiner H, Bartsch G, Hobisch A. Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem. 2005;95:497–505.
- Gupta J, Mitra N, Kanetsky PA, et al. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephrol. 2012;7:1938–1946.
- Shankar A, Sun L, Klein BE, et al. Markers of inflammation predict the long-term risk of developing chronic kidney disease: A population-based cohort study. Kidney Int. 2011;80:1231–1238.
- Sikorska D, Szkudlarek M, Kłysz P, et al. Cross-sectional assessment of relationship between the stage of chronic kidney disease, chronic inflammation indicators and selected markers of cardiovascular damage. Now Lek. 2013;82:197–203.
- Oberg BP, Mc Menamin E, Lucas FL, et al. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004;65:1009–1016.
- Janeczko M, Niedzielska E, Pietras W. Evaluation of renal function in pediatric patients after treatment for Wilms’ tumor. Adv Clin Exp Med. 2015;24:497–504.
- Portilla D, Dent C, Sugaya T, et al. Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2008;73:465–472.
- Yang J, Choi HM, Seo MY, et al. Urine liver-type fatty acid-binding protein predicts graft outcome up to 2 years after kidney transplantation. Transplant Proc. 2014;46:376–380.
- Krawczeski CD, Goldstein SL, Woo JG, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58:2301–2309.
- Hwang YJ, Hyun MC, Choi BS, Chun SY, Cho MH. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease. J Korean Med Sci. 2014;29:1102–1107.
- Kamijo A, Sugaya T, Hikawa A, et al. Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol Cell Biochem. 2006;284:175–182.
- Xie Y, Xue W, Shao X, et al. Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes. PLoS One. 2014;9: e112865. https://doi.org/10.1371/journal.pone.0112865
- Kamijo A, Sugaya T, Hikawa A, 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;145:125–133.
- Kamijo-Ikemori A, Sugaya T, Sekizuka A, Hirata K, Kimura K. Amelioration of diabetic tubulointerstitial damage in liver-type fatty acid-binding protein transgenic mice. Nephrol Dial Transplant. 2009;24: 788–800.
- Panduru NM, Forsblom C, Saraheimo M; FinnDiane Study Group, et al. Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care. 2013;36: 2077–2083.
- 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;413:187–191.
- Sato R, Suzuki Y, Takahashi G, Kojika M, Inoue Y, Endo S. A newly developed kit for the measurement of urinary liver-type fatty acid-binding protein as a biomarker for acute kidney injury in patients with critical care. J Infect Chemother. 2015;21:165–169.
- Zajączkowska MM, Bieniaś B. Aktualny stan wiedzy na temat patogenezy, diagnostyki i leczenia przewlekłej choroby nerek. Med Og Nauk Zdr. 2013;19:1–7.
- Perlman AS, Chevalier JM, Wilkinson P, et al. Serum inflammatory and immune mediators are elevated in early stage diabetic nephropathy. Ann Clin Lab Sci. 2015;45:256–263.
- Rodríguez LM, Robles B, Marugán JM, et al. Do serum C-reactive protein and interleukin-6 predict kidney scarring after urinary tract infection? Indian J Pediatr. 2013;80:1002–1006.
- Dennen P, Altmann C, Kaufman J, et al. Urine interleukin-6 is an early biomarker of acute kidney injury in children undergoing cardiac surgery. Crit Care. 2010;14:R181.
- Greenberg JH, Whitlock R, Zhang WR, et al. Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery. Pediatr Nephrol. 2015;30:1519–1527.
- Zhang WR, Garg AX, Coca SG, et al. Plasma IL-6 and IL-10 concentrations predict AKI and long-term mortality in adults after cardiac surgery. J Am Soc Nephrol. 2015;26:3123–3132.
- Miklaszewska M, Korohoda P, Zachwieja K, et al. Serum interleukin 6 levels as an early marker of acute kidney injury on children after cardiac surgery. Adv Clin Exp Med. 2013;22:377–386.