Citation Information :
Padwal MK, Raichurkar AV, Melinkeri RR. Serum Ferritin Levels in Patients of Chronic Kidney Disease on Hemodialysis: A Need to Redefine Cutoff for Iron/Erythropoietin Therapy. Indian J Med Biochem 2018; 22 (2):95-99.
Introduction: Anemia is the common complication of chronic kidney disease (CKD) that mainly affects patients on hemodialysis therapy. The most precise tool to evaluate body iron stores is the measurement of serum ferritin levels. However, serum ferritin is also an acute phase reactant, and its levels may be influenced by inflammation.
Objectives: (1) To measure serum ferritin and C-reactive protein (CRP) in the study group; (2) To correlate the levels of serum ferritin and CRP in patients on hemodialysis; (3) To establish a cutoff value for serum ferritin in patients of CKD on hemodialysis receiving Iron/EPO therapy.
Materials and methods: The study participants (n = 240) were divided into three groups as group I: Total 80 cases of CKD on hemodialysis receiving iron/erythropoietin (EPO) therapy, Group II: Total 80 cases of CKD on hemodialysis not receiving iron/erythropoietin (EPO) therapy, and Group III: Age and gender-matched 80 healthy controls. Estimation of serum ferritin was done by automated chemiluminescent microparticle immunoassay (CMIA) and CRP by immunoturbidimetric technique.
Results: We observed a statistically significant rise in serum ferritin Group I (1957.6 ± 714.1), Group II (1063.5 ± 478.6) as compared to Group III (101.21 ± 60.29) and CRP levels in group I (104.6 ± 70.8) as compared to group II(74.9 ± 55.8) and (3.7 ± 0.9) (p < 0.005).There is a significant positive correlation between ferritin and CRP (p < 0.005).
Conclusion: High ferritin levels can be because of both increased iron stores and inflammation which may be associated with erythropoietin resistance, malnutrition, and increased mortality. A cutoff value of ferritin needs to be established for better interpretation.
Joanne M, Skorecki BK. Disorders of the Kidney and Urinary Tract: Longo Fauci and Kasper Hauser. Harrison's Principles of Internal Medicine 18th ed. Part 13 Chapter 280 Chronic Kidney Disease. The McGraw-Hill companies. 2011;2: 2308-2316.
Levey AS, Coresh J, Bolton K, Culleton B, Harvey KS, Ikizler TA, et al. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. American Journal of Kidney Diseases. 2002 Feb;39(2 SUPPL. 1): S1-S266.
Kalender B, Mutlu B, Ersoz M, Kalkan A, Yilmaz A. The effects of acute phase proteins on serum albumin, transferrin and haemoglobin in haemodialysis patients. Int J ClinPract. 2002; 56:505-508
Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity of mortality in hemodialysis patients. American Journal of Kidney Diseases [Internet]. Elsevier BV; 2001 Mar;37(3):564-572.
Rogers JT. Ferritin translation by interleukin-1and interleukin- 6: the role of sequences upstream of the start codons of the heavy and light subunit genes. Blood. 1996;87:2525-2537.
Kalantar-Zadeh K, Ikizler A, Block G, Avram M, Kopple J. Malnutrition–inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis. Am J Kidney Dis. 2003 Nov;42(5):864-881.
Kalantar-Zadeh K, Hoffken B, Wunsch H, Fink H, Kleiner M, Luft FC. Diagnosis of iron deficiency anemia in renal failure patients during the post erythropoietin era. Am J Kidney Dis 1995;26:292-299.
Ong DS, Wang L, Zhu Y, Ho B, Ding JL.”The response of ferritin to LPS and acute phase of Pseudomonas infection. Journal of Endotoxin Research. 2005;11(5):267-280.
Krause JR, Stolc V. Serum Ferritin and Bone Marrow Iron Stores, Correlation with Absence of Iron in Biopsy Specimens. Am J Clin Pathol. 1979;72:817-820.
Kalantar-Zadeh K, Rodriguez RA, Humphreys MH. Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant. 2004;34:141-149.
Smith J, Osikowicz G. Abbott AxSYM random and continuous access immunoassay system for improved workflow in the clinical laboratory. Clinical chemistry. 1993 Oct 1;39(10): 2063-2069.
Siedel J, Wahlefeld AW, Ziegenhorn J. A new iron Ferrozine reagent without deproteinization. Clin Chem. 1984;30:975.
Maruyama Y, Yokoyama K. The Different Association between Serum Ferritin and Mortality in Hemodialysis and Peritoneal Dialysis Patients Using Japanese Nationwide Dialysis Registry. PLoS One. 2015;10(11):e0143430.
Gunnell J, Yeun JY, Depner TA, Kaysen GA. Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. American Journal of Kidney Diseases [Internet]. Elsevier BV; 1999 Jan;33(1):63-72.
Jennifer Gunnell, MD, Jane Y. Yeun. Acute-Phase Response Predicts Erythropoietin Resistance inHemodialysis and Peritoneal Dialysis PatientsAmerican Journal of Kidney Diseases. 1999;33(1):63-72.
Akchurin OM, Kaskel F. Update on Inflammation in Chronic Kidney Disease. Blood Purification [Internet]. S. Karger AG; 2015 Jan 20;39(1-3):84-92.
Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN. Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. J Biol Chem. 1990 Aug 25;265(24):14572-14578.
Kim HJ, Vaziri ND. Contribution of impaired Nrf2-Keap1 pathway to oxidative stress and inflammation in chronic renal failure. American Journal of Physiology-Renal Physiology [Internet]. American Physiological Society; 2010 Mar;298(3): F662-F671.
Nassar GM. Preventing and Treating Inflammation: Role of Dialysis Access Management. Seminars in Dialysis [Internet]. Wiley; 2012 Oct 9;26(1):28-30.
Friedrich B, Alexander D, Janessa A, Häring H-U, Lang F, Risler T. Acute effects of hemodialysis on cytokine transcription profiles: Evidence for C-reactive protein-dependency of mediator induction. Kidney International [Internet]. Elsevier BV; 2006 Dec;70(12):2124–2130.