Survey of serum iron and ferritin concentrations in patients with stage 3 to 5 chronic kidney disease

Nội dung text: Survey of serum iron and ferritin concentrations in patients with stage 3 to 5 chronic kidney disease

1. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 SURVEY OF SERUM IRON AND FERRITIN CONCENTRATIONS IN PATIENTS WITH STAGE 3 TO 5 CHRONIC KIDNEY DISEASE Nguyen Van Hung*; Nguyen Cao Luan**; Le Viet Thang*** SUMMARY Objectives: To evaluate the serum iron and ferritin concentrations in patients with chronic kidney disease (CKD) predialysis and its relation with stages of CKD and some other features. Subjects and methods: A cross-sectional study on a group of 175 patients with CKD stage 3 - 5 and a control group of 51 healthy people at Department of Nephrology and Hemodialysis, 103 Military Hospital. Results: The average concentrations of serum iron in study group was significantly lower than control group (12.87 ± 6.85 µmol/L versus 16.57 ± 5.83 µmol/L), but the average concentrations of serum ferritin in study group was higher than in the control group (308.59 ± 178.41 ng/mL versus 159.89 ± 87.98 ng/mL) with p < 0.01. Serum iron and ferritin concentrations were significantly associated with the stages of CKD (p < 0.05). Ferritin levels were positively correlated with serum creatinine levels (r = 0.256; p < 0.01) and hs-CRP levels (r = 0.383; p < 0.001). Conclusion: Patients with stage 3 - 5 CKD, predialysis had lower serum iron and higher serum ferritin concentrations compared to control group. There was significant correlation between serum iron, ferritin with serum creatinine concentrations and hs-CRP levels. * Keywords: Chronic kidney disease; Serum iron; Serum ferritin; Predialysis. INTRODUCTION of iron ultimately lead to absolute or functional iron deficiency anaemia. Anaemia of end- Chronic kidney disease is a worldwide stage renal disease can be managed public health problem with an increasing successfully by recombinant human incidence and prevalence, poor outcomes EPO. Iron administration plays a central and high cost. Chronic kidney disease role in enhancing anaemia responsiveness causes not only kidney failure but also to EPO. Serum ferritin concentrations and complications of decreased kidney function iron saturation ratio are among the two most and cardiovascular disease [5]. commonly used markers of iron status in Anaemia of chronic kidney disease (CKD) maintenance dialysis patients [4]. is widely common in patients with renal Absolute iron deficiency, the iron impairment and is associated with significant deficiency that is characterized by low morbidity and mortality. Deficient erythropoietin orabsent bone marrow staining for iron, (EPO) production and reduced bioavailability is to be distinguished from functional or * Transport Hospital ** Bachmai Hospital ** 103 Military Hospital Corresponding author: Nguyen Van Hung (hunggttw@gmail.com) Date received: 04/10/2017 Date accepted: 22/11/2017 163
2. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 relative iron deficiency, which is defined within last 7 days; did not agree to participate as a response to intravenous iron with an in the study. increase in hemoglobin (Hb) or a decrease 2. Methods. in erythropoiesis-stimulating agent (ESA) * Study design: A cross-sectional requirement [8]. Therefore, we conducted descriptive study. this research aiming: To assess the serum iron and ferritin concentrations in - Serum iron concentrations measurement: patients with stage 3 - 5 CKD and its Quantification of serum iron concentrations relation with stages of CKD, serum creatinine by color comparison following the principle: 3+ concentrations and hs-CRP. Fe is released from the transferrin-Fe 3+ SUBJECTS AND METHODS complex at pH < 2.0; Fe in the acid environment will be reduced to Fe2+. Fe2+ 1. Subjects. combined with ferrozine buffers to form a The study was conducted on a group color complex. After that, the test is conducted of 175 patients with CKD stage 3 - 5, on the Cobas 6,000 system with Roche's predialysis and a control group of 51 healthy kit. people at Department of Nephrology and - Serum ferritin concentrations Hemodialysis, 103 Military Hospital. measurement: Quantification of serum * Excluding criteria: Blood transfusion, ferritin by immunohistochemistry on the acute bleeding, some acute diseases, Cobas 6,000 system with Roche's kit. being performed surgery within 3 months * Diagnostic criteria: prior to study period; taking iron products Table 1: Stages of CKD: K/DOQI 2002 [1]. Stage Description GFR (mL/min/1.73m2) 1 Kidney damage with normal or increase GFR ≥ 90 2 Kidney damage with mild decrease GFR 60 - 90 3 Moderate decrease GFR 30 - 59 4 Severe decrease GFR 15 - 29 5 Kidney failure < 15 (or dialysis) - Serum hs-CRP > 5 mg/L: diagnosed as increase. * Statistical analysis: Statistical analyses were conducted using SPSS 20.0. 164
3. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 RESULTS AND DISCUSSION The study group with an average age of 53.26 years old, 69.1% male, 30.9% female. There was not significant difference compared to those of control group. Table 2: Iron and ferritin concentrations between study group and control group. Indexes Control group (n = 51) Study group (n = 175) p average 16.57 ± 5.83 12.87 ± 6.85 < 0.01 Iron* (µmoL/L) min 7.8 2.0 max 41.8 38.7 average 159.89 ± 87.98 308.59 ± 178.41 < 0.001 Ferritin* (ng/mL) min 10.6 35.1 max 501.8 698.6 In our study, the average concentrations weight of about 450 kDa, containing of serum iron in study group was significant heavy (H) and light (L) subunits. Serum lower than control group (12.87 µmol/L ferritin is slightly different than tissue versus 16.57 µmol/L) with p < 0.01. The ferritin and contains little or no iron. While average concentrations of serum ferritin in tissue ferritin clearly plays a role in study group was higher than in the control intracellular iron handling, the role of group with p < 0.01 (308.59 ng/mL versus serum ferritin is less clearly understood. 159.89 ng/mL). The study by Malyszko J The level of ferritin in plasma represents also showed that the average concentrations the balance between its secretion, which of serum iron and ferritin in chronic kidney is directly related to intracellular iron synthesis failure was significantly lower than control and its clearance, mainly in liver and other group (with p < 0.05 and 0.001, respectively) organs [3]. However, liver dysfunction and [7]. Serum ferritin is a frequently used inflammatory factors may interfere with marker of iron status in CKD patients. the synthesis and clearance of ferritin, Serum ferritin concentration results from thereby increasing serum ferritin levels the leakage of tissue ferritin, an intracellular due to circumstances unrelated to iron iron storage protein shell with a molecular metabolism. 165
4. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 Table 3: Relationship between iron, ferritin concentrations and stages of CKD in study group (n = 175). Stages of CKD Iron (µmol/L) X ± 2SD Ferritin (ng/mL) ± 2SD 3 (n = 31) 16.31 ± 6.56 197.46 ± 50.85 4 (n = 35) 13.88 ± 6.26 261.70 ± 141.19 5 (n = 109) 11.57 ± 6.77 355.25 ± 194.51 pANOVA < 0.01 < 0.001 Our results showed that serum iron and ferritin concentrations were significantly associated with the stages of CKD (p < 0.01). Patients with stage 3 CKD had the highest levels of serum iron and the lowest levels of serum ferritin, while the patients with stage 5 CKD had the lowest iron concentrations and the highest serum ferritin concentrations. Table 4: Correlation between serum iron, ferritin concentrations and serum creatinine (n = 175). Creatinine (µmol/l) Indexes Correlation equation r p Iron (µmol/L) -0.103 > 0.05 Ferritin (ng/mL) 0.256 < 0.01 Ferritin = 0.121 x creatinine + 240.46 Serum iron concentrations was not ferritin for progressively lower levels of correlated with serum creatinine renal function (p < 0.0001) [2]. Iron is a concentrations, whereas ferritin levels vital element for numerous body functions, were positively correlated with serum most notably as an ingredient of hemoglobin creatinine levels (r = 0.256; p < 0.01). Our (Hb). Most healthy people can achieve a results in table 3 and 4 showed that stable iron balance, managing to ingest serum iron and ferritin concentrations the required amount of iron in the diet were significantly associated with the to compensate for the small amount of stage of CKD as well as the serum daily loss iron from the gut. However, creatinine concentration. These results many patients with advanced CKD were similar to those by Fishbane S’ are in negative iron balance as a result (the same subjects): among women, there of reduced dietary intake, impaired was a trend toward lower decreasing absorption from the gut and increased mean TSAT for progressively lower levels loss iron, so serum iron concentrations of renal function (p < 0.02) and a statistically mostly decreased. In our study, there significant trend toward increasing serum was an increase in serum ferritin 166
5. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 concentrations. It is likely due to the a profound effect on iron indices. effect of inflammation. It is well known Previously, in hemodialysis, hs-CRP, that occult inflammation is commonly an indicator of inflammation, was found to present in CKD and may increase withX be highly correlated with serum ferritin progressive disease [6]. Inflammation has values [2]. Ferritin = 0.121xCreatinine + 240.46 800 700 600 500 400 Ferritin 300 200 100 0 Creatinine 0 500 1000 1500 2000 2500 Chart 1: Correlation between serum ferritin concentration and serum creatinine. Table 5: Relationship between serum iron, ferritin concentrations and hs-CRP (n = 175). hs-CRP status Iron (µmol/L) ± 2SD Ferritin (ng/mL) ± 2SD hs-CRP > 5 mg/L (n = 52) 11.71 ± 6.97 411.03 ± 177.65 hs-CRP ≤ 5 mg/L (n = 123) 13.36 ± 6.77 265.28 ± 160.75 p > 0.05 < 0.001 In patients with elevated hs-CRP levels, serum iron concentrations were significantly lower than those without elevated hs-CRP, but the difference was not statistically significant (p > 0.05). By contrast, serum ferritin concentrations in patients who elevated hs-CRP was significantly higher than non elevated hs-CRP group with p < 0.001. 167
6. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 Table 6: Correlation between serum iron, ferritin concentrations and hs-CRP (n = 175). hs-CRP (mg/l) Indexes Correlation equation r p Iron (µmol/L) -0.117 > 0.05 Ferritin (ng/mL) 0.383 < 0.001 Ferritin = 23.52 x CRP + 223.26 There was no correlation between serum iron concentrations and hs-CRP levels, but there was a positive correlation between ferritin and hs-CRP levels (r = 0.383; p < 0.001). Ferritin = 0.121xCreatinine + 240.46 800 700 600 500 400 Ferritin 300 200 100 0 Creatinine 0 500 1000 1500 2000 2500 Chart 2: Correlation between serum ferritin concentration and hs-CRP. In table 5 and 6, we found that serum atherosclerosis. It also blunts the iron ferritin concentration in patients who elevated utilization and induces resistance to hs-CRP was significantly higher than non erythropoietin therapy. The exact pathway elevated hs-CRP group and there was a which the inflammatory cascade results in positive correlation between ferritin and erythropoietin resistance is not completely hs-CRP levels. The study by Kalantar- understood. It has been hypothesized that Zadeh K. also showed that there was a inflammatory activators have a pro-apoptotic possitive correlation between serum ferritin effect on erythroid progenitor cells and and serum hs-CRP concentration (r = 0.31; compete with the anti-apoptotic effect of p = 0.005) [4]. Inflammation has been erythropoietin, the end result being implicated in several complications in CKD, erythropoietin resistance. Serum ferritin is including malnutrition and accelerated also an acute phase reactant which may 168
7. JOURNAL OF MILITARY PHARMACO-MEDICINE N09-2017 also be elevated during an inflammation. 2. Fishbane S et al. Iron indices in chronic Thus, an elevation of serum ferritin can be kidney disease in National Health and Nutritional due to an increase in body iron stores or Examination Survey 1988 - 2004. Clin J Am an inflammation, both of which are hazardous Soc Nephrol. 2009. 4 (1), pp.57-61. in patients with CKD. 3. Kalantar-Zadeh K et al. Serum ferritin is a marker of morbidity and mortality in CONCLUSIONS hemodialysis patients. Am J Kidney Dis. 2001, 37 (3), pp.564-572. In our study, the average concentration 4. Kalantar-Zadeh K, R.A. Rodriguez, M.H. of serum iron in study group was significantly Humphreys. Association between serum lower than that in the control group (12.87 ± ferritin and measures of inflammation, nutrition 6.85 µmol/L versus 16.57 ± 5.83 µmol/L), and iron in haemodialysis patients. Nephrol but the average concentration of serum Dial Transplant. 2004. 19 (1), pp.141-149. ferritin in study group was higher than that in 5. Krishnan A et al. Anaemia of chronic the control group (308.59 ± 178.41 ng/mL kidney disease: What We Know Now. 2017, versus 159.89 ± 87.98 ng/mL) with p < 0.01. Vol 1, 11. Serum iron and ferritin concentrations were 6. Landray M.J et al. Inflammation, significantly associated with the stages of endothelial dysfunction and platelet activation CKD (p < 0.01). Ferritin levels were positively in patients with chronic kidney disease: the correlated with serum creatinine levels chronic renal impairment in Birmingham (r = 0.256; p < 0.01) and hs-CRP levels (CRIB) study. Am J Kidney Dis. 2004, 43 (2), (r = 0.383; p < 0.001). pp.244-253. 7. Malyszko J et al. Hepcidin, iron status and renal function in chronic renal failure, REFFERENCES kidney transplantation and hemodialysis. Am 1. K/DOQI clinical practice guidelines for J Hematol. 2006, 81 (11), pp.832-837. chronic kidney disease: evaluation, classification, 8. Wish J.B. Assessing iron status: beyond and stratification. Am J Kidney Dis. 2002. 39 serum ferritin and transferrin saturation. Clin J (2 Suppl 1), pp.S1-266. Am Soc Nephrol. 2006, 1, Suppl 1, pp.S4-S8. 169