Hepcidin and its Related Hematological Biomarkers of Anemia in Children on Hemodialysis: Role of Carnitine Deficiency

  • Safinaz E. El-Toukhy Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
  • Fatina Fadel Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
  • Manal Elshamaa Department of Pediatrics, National Research Centre, Cairo, Egypt
  • Gamila S. M. El-Saeed Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
  • Hanan Abdelaziz Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt
  • Marwa Elsonbaty Department of Child Health, Medical Research Division, National Research Centre (Affiliation ID: 60014618), Cairo, Egypt; Department of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Kingdom of Saudi Arabia
  • Eman A. Elghoroury Department of Clinical and Chemical Pathology, National Research Centre, Cairo, Egypt
  • Eman Hamza Department of Clinical and Chemical Pathology, National Research Centre, Cairo, Egypt
  • Soha Atef Department of Clinical and Chemical Pathology, National Research Centre, Cairo, Egypt
Keywords: Hepcidin, High-sensitivity C-reactive protein, Carnitine, Anemia, Inflammation, Children, Hemodialysis

Abstract

BACKGROUND: Anemia is one of the most common complications in end-stage renal disease (ESRD) patients. Hepcidin is a hormone that regulates iron homeostasis in patients with ESRD. Carnitine deficiency is commonly seen in hemodialysis (HD) patients.

AIM: This study aimed to investigate the relationship between hepcidin and inflammatory and other anemia markers in children with ESRD and to evaluate the association of carnitine deficiency with anemia in these patients.

SUBJECTS AND METHODS: Thirty pediatric patients with ESRD undergoing HD, and thirty healthy, age- and sex-matched children served as controls were included in the study. Serum levels hepcidin, iron status, high-sensitivity C-reactive protein, and total carnitine were measured.

RESULTS: Statistically significant increases in serum levels of hepcidin (100.7 ± 0.99 ng\ml vs. 77.43 ± 0.8 ng\ml, p = 0.000), was found in HD children as compared to healthy controls. Statistically significant increase in serum levels of hs-CRP (3.94 ± 0.19 mg/l vs. 1.36 ± 0.07 mg/l, p = 0.04) was found in HD children as compared to healthy controls. However, serum levels of carnitine (29.59 ± 2.46 μmol/L vs. 36 ± 2.39 μmol/L, p = 0.000) showed statistically significant decreases in HD children as compared to healthy controls positive correlation was found between hepcidin and hs-CRP (r = 0.059, p = 0.042). Furthermore, a positive correlation was present between serum carnitine levels and serum iron levels (r = 0.651, p = 0.042).

CONCLUSION: Serum hepcidin may be a more useful biomarker of functional iron deficiency in children on HD. The efficacy of carnitine treatment for children on HD with carnitine deficiency and its effect on anemia needs to be studied.

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References

Horl WH. Anemia as a risk factor for chronic kidney disease. Arch Med Sci. 2009;5(3A):S421-8.

Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: The third national health and nutrition examination survey (1988-1994). Arch Intern Med. 2002;162(12):1401-8. https://doi.org/10.1001/ archinte.162.12.1401 PMid:12076240

Dowling TC. Prevalence, etiology, and consequences of anemia and clinical and economic benefits of anemia correction in patients with chronic kidney disease: An overview. Am J Health Syst Pharm. 2007;64(8):3-7. https://doi.org/10.2146/ ajhp070181 PMid:17591994

KDOQI. KDOQI Clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: 2007 Update of hemoglobin target. Am J Kidney Dis. 2007;50(3):471- 530. https://doi.org/10.1053/j.ajkd.2007.06.008 PMid:17720528

Fassett RG, Driver R, Healy H, Ranganathan D, Ratanjee S, Robertson IK, et al. Comparison of markers of oxidative stress, inflammation and arterial stiffness between incident hemodialysis and peritoneal dialysis patients-an observational study. BMC Nephrol. 2009;10:8. https://doi.org/10.1186/1471-2369-10-8 PMid:19284599

Vaziri N. Anemia and anemia correction: Surrogate markers or causes of morbidity in chronic kidney disease? Nat Clin Pract Nephrol. 2008;4(8):436-45. https://doi.org/10.1038/ ncpneph0847

Preza GC, Pinon R, Ganz T, Nemeth E. Cellular catabolism of the iron-regulatory peptide hormone hepcidin. PLoS One. 2013;8(3):e58934. https://doi.org/10.1371/journal. pone.0058934

Berberat PO, Katori M, Kaczmarek E, Anselmo D, Lassman C, Ke B, et al. Heavy chain ferritin acts as an antiapoptotic gene that protects liversfrom ischemia reperfusion injury. FASEB J. 2003;17(12):1724-6. https://doi.org/10.1096/fj.03-0229fje PMid:12958189

Arkadopoulos N, Nastos C, Kalimeris K, Economou E, Theodoraki K, Kouskouni E, et al. Iron chelation for amelioration of liver ischemia-reperfusion injury. Hemoglobin. 2010;34(3):265- 77. https://doi.org/10.3109/03630269.2010.484766 PMid:20524816

Won HS, Kim HG, Yun YS, Jeon EK, Ko YH, Kim YS. IL-6 is an independent risk factor for resistance to erythropoiesis-stimulating agents in hemodialysis patients without iron deficiency. Hemodial Int. 2012;16(1):31-7. https://doi. org/10.1111/j.1542-4758.2011.00635.x PMid:22284696

Panichi V, Maggiore U, Taccola D, Migliori M, Rizza GM, Consani C, et al. Interleukin-6 is a stronger predictor of total and cardiovascular mortality than C-reactive protein in haemodialysis patients. Nephrol Dial Transplant. 2004;19(5):1154-60. https:// doi.org/10.1093/ndt/gfh052 PMid:14993508

Zaritsky J, Young B, Wang HJ, Westerman M, Olbina G, Nemeth E, et al. Hepcidin-a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(6):1051-6. https://doi.org/10.2215/cjn.05931108 PMid:19406957

Zaritsky J, Young B, Gales B, Wang HJ, Rastogi A, Westerman M, et al. Reduction of serum hepcidin by hemodialysis in pediatric and adult patients. Clin J Am Soc Nephrol. 2010;5(6):1010-4. https://doi.org/10.2215/cjn.08161109 PMid:20299375

Rubab Z, Amin H, Abbas K, Hussain S, Ullah MI, Mohsin S. Serum hepcidin levels in patients with end-stage renal disease on hemodialysis. Saudi J Kidney Dis Transpl. 2015;26(1):19-25. https://doi.org/10.4103/1319-2442.148716 PMid:25579711

Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631-4. PMid:22935483

Ganz T, Nemeth E. Iron balance and the role of hepcidin in chronic kidney disease. Semin Nephrol. 2016;36(2):87-93. PMid:27236128

Kaneko S, Hirai K, Morino J, Minato S, Yanai K, Mutsuyoshi Y, et al. Association between carnitine deficiency and the erythropoietin resistance index in patients undergoing peritoneal dialysis: A cross-sectional observational study. Ren Fail. 2020,42(1):146- 53. https://doi.org/10.1080/0886022x.2020.1719847 PMid:32003308

Kamei D, Tsuchiya K, Nitta K, Mineshima M, Akiba T. Association between resistance to erythropoiesis-stimulating agents and carnitine profile in patients on maintenance haemodialysis. Nephrology (Carlton). 2018;23(8):737-43. https://doi. org/10.1111/nep.13079 PMid:28608940

Zhang YM, Zhuo L, Hu J, Cui G, Zhang L, Zhang XL, et al. Clinical significance of different carnitine levels for improving the prognosis of patients undergoing hemodialysis. Ren Fail. 2016;38(10):1654-8. https://doi.org/10.1080/08860 22x.2016.1229967 PMid:27758157

Hatanaka Y, Higuchi T, Akiya Y, Horikami T, Tei R, Furukawa T, et al. Prevalence of carnitine deficiency and decreased carnitine levels in patients on hemodialysis. Blood Purif. 2019;47(2):38- 44. https://doi.org/10.1159/000496720 PMid:30943487

Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA. 2002;99(7):4596-601. https://doi.org/10.1073/ pnas.072632499 PMid:11930010

Atkinson M, Kim J, Roy C, Warady BA, White CT, Furth SL. Hepcidin and risk of anemia in CKD: A cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol. 2015;30(4):635-43. https://doi.org/10.1007/s00467-014-2991-4 PMid:25380788

Mercadel L, Metzger M, Haymann JP, Thervet E, Boffa JJ, Flamant M, et al. The relation of hepcidin to iron disorders, inflammation and hemoglobin in chronic kidney disease. PLoS One. 2014;9(6):e99781. https://doi.org/10.1371/journal. pone.0099781 PMid:24978810

Troutt JS, Butterfield AM, Konrad RJ. Hepcidin-25 concentrations are markedly increased in patients with chronic kidney disease and are inversely correlated with estimated glomerular filtration rates. J Clin Lab Anal. 2013;27(6):504-10. https://doi. org/10.1002/jcla.21634 PMid:24218134

Minutolo R, Locatelli F, Gallieni M, Bonofiglio R, Fuiano G, Oldrizzi L, et al. Anaemia management in non-dialysis chronic kidney disease (CKD) patients: A multicentre prospective study in renal clinics. Nephrol Dial Transplant. 2013;28(12):3035-45. https://doi.org/10.1093/ndt/gft338

Sohal AS, Gangji AS, Crowther MA, Treleaven D. Uremic bleeding: Pathophysiology and clinical risk factors. Thromb Res. 2006;118(3):417-22. https://doi.org/10.1016/j. thromres.2005.03.032 PMid:15993929

Scindia Y, Dey P, Thirunagari A, Liping H, Rosin D, Floris M, et al. Hepcidin mitigates renal ischemia-reperfusion injury by modulating systemic iron homeostasis. J Am Soc Nephrol. 2015;26(11):2800-14. https://doi.org/10.1681/asn.2014101037 PMid:25788528

Cohen LA, Gutierrez L, Weiss A, Bardoogo YL, Zhang D, Crooks DR, et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood. 2010;116(9):1574-84. https://doi.org/10.1182/ blood-2009-11-253815 PMid:20472835

Sancho A, Pastor MC, Troya M, Bonal J, Bayés B, Morales- Indiano C, et al. Hepcidin and iron deficiency in pre-kidney transplant patients. Transplant Proc. 2009;41(6):2079-81. https://doi.org/10.1016/j.transproceed.2009.06.089 PMid:19715836

Costa E, Rocha S, Rocha-Pereira P, Nascimento H, Castro E, Miranda V, et al. Neutrophil activation and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Am J Nephrol. 2008;28(6):935-40. https://doi. org/10.1159/000142147 PMid:18587235

Marín VB, Azocar M, Molina M, Guerrero JL, Ratner R, Cano F. Total carnitine and acylated carnitine ratio: Relationship of free carnitine with lipid parameters in pediatric dialysis patients. Adv Perit Dial. 2006;22:130-5. PMid:16983956

Guarnieri G, Situlin R, Biolo G. Carnitine metabolism in uremia. Am J Kidney Dis. 2001,38(1):S63-7. https://doi.org/10.1053/ ajkd.2001.27408 PMid:11576925

Bonomini M, Zammit V, Pusey CD, Vecchi AD, Arduini A. Pharmacological use of L-carnitine in uremic anemia: has its full potential been exploited? Pharmacol Res. 2011;63(3):157-64. https://doi.org/10.1016/j.phrs.2010.11.006 PMid:21138768

Kudoh Y, Aoyama S, Torii T, Chen Q, Nagahara D, Sakata H, et al. Long-term effects of oral L-carnitine supplementation on anemia in chronic hemodialysis. Cardiorenal Med. 2014;4(1):53- 9. https://doi.org/10.1159/000360865 PMid:24847334

Eknoyan G, Latos DL, Lindberg J. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National kidney foundation carnitine consensus conference. Am J Kidney Dis. 2003;41(4):868-76. https://doi.org/10.1016/ s0272-6386(03)00110-0 PMid:12666074

Published
2020-06-20
How to Cite
1.
El-Toukhy SE, Fadel F, Elshamaa M, El-Saeed GSM, Abdelaziz H, Elsonbaty M, Elghoroury EA, Hamza E, Atef S. Hepcidin and its Related Hematological Biomarkers of Anemia in Children on Hemodialysis: Role of Carnitine Deficiency. Open Access Maced J Med Sci [Internet]. 2020Jun.20 [cited 2020Oct.31];8(B):524-9. Available from: https://www.id-press.eu/mjms/article/view/4268

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