Hepcidin and proinflammatory markers in children with chronic kidney disease : A case-control study
BACKGROUND: Hepcidin is the main regulator of hepcidin-ferroportin axis and is elevated in children with chronic kidney disease (CKD). Anemia of CKD and its relation to hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in iron- and erythropoietin (EPO)-naïve, non-dialyzed children with CKD is under-studied.
MATERIALS AND METHODS: This case-control study aimed to study the levels of hepcidin and other proinflammatory markers (IL-6, TNF-α, hs-CRP) and their relation with anemia in iron- and erythropoietin-naïve, non-dialysis CKD (stage 3 - 5) patients. 32 pediatric CKD stage 3 - 5 patients aged 2 - 18 years without previous iron or EPO therapy were compared with 32 gender- and age-matched healthy controls. The CKD cases were also divided into three categories based on their serum ferritin levels and transferrin saturation (%TSAT): true iron deficiency, impaired iron trafficking, and no iron deficiency. The baseline iron status was then correlated with the serum hepcidin levels.
RESULTS: Serum hepcidin, IL-6, and TNF-α levels were significantly elevated compared to controls. As CKD stage progressed, hemoglobin levels decreased, while serum hepcidin, IL6, TNF-α and hs-CRP levels increased significantly. Serum hepcidin levels correlated positively with IL-6 (r = 0.57, p = 0.001), TNF-α (r = 0.34, p = 0.05), hs-CRP (r = 0.36, p = 0.03), and ferritin (r = 0.07, p = 0.001), while being inversely correlated with Total iron binding capacity (TIBC) (r = -0.50, p = 0.003), hemoglobin (r = -0.52, p = 0.001), and glomerular filtration rate (GFR) (r = -0.71, p = 0.000). Serum hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency (55.16 vs. 49 vs. 11.8, p = 0.005). Amongst those with no iron deficiency, hepcidin correlated negatively with hemoglobin (r = -0.752, p-value = 0.007).
CONCLUSION: A positive correlation between hepcidin and other inflammatory biomarkers in non-dialyzed, iron- and EPO-naïve pediatric CKD patients suggests a role of these markers in higher hepcidin production and its contribution to iron-restricted erythropoiesis across the spectrum of CKD. Median hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency, suggesting that in an iron-replete state, high hepcidin levels inhibit iron absorption from the gut and release from iron storing cells, thus restricting erythropoiesis leading to anemia.
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| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
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| Enthalten in: |
Clinical nephrology - 89(2018), 5 vom: 16. Mai, Seite 363-370 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Goyal, Kamal Kumar [VerfasserIn] |
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| Links: |
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| Themen: |
9007-41-4 |
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| Anmerkungen: |
Date Completed 20.08.2018 Date Revised 08.04.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.5414/CN109132 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM281100365 |
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| 100 | 1 | |a Goyal, Kamal Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hepcidin and proinflammatory markers in children with chronic kidney disease |b A case-control study |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 20.08.2018 | ||
| 500 | |a Date Revised 08.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Hepcidin is the main regulator of hepcidin-ferroportin axis and is elevated in children with chronic kidney disease (CKD). Anemia of CKD and its relation to hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in iron- and erythropoietin (EPO)-naïve, non-dialyzed children with CKD is under-studied | ||
| 520 | |a MATERIALS AND METHODS: This case-control study aimed to study the levels of hepcidin and other proinflammatory markers (IL-6, TNF-α, hs-CRP) and their relation with anemia in iron- and erythropoietin-naïve, non-dialysis CKD (stage 3 - 5) patients. 32 pediatric CKD stage 3 - 5 patients aged 2 - 18 years without previous iron or EPO therapy were compared with 32 gender- and age-matched healthy controls. The CKD cases were also divided into three categories based on their serum ferritin levels and transferrin saturation (%TSAT): true iron deficiency, impaired iron trafficking, and no iron deficiency. The baseline iron status was then correlated with the serum hepcidin levels | ||
| 520 | |a RESULTS: Serum hepcidin, IL-6, and TNF-α levels were significantly elevated compared to controls. As CKD stage progressed, hemoglobin levels decreased, while serum hepcidin, IL6, TNF-α and hs-CRP levels increased significantly. Serum hepcidin levels correlated positively with IL-6 (r = 0.57, p = 0.001), TNF-α (r = 0.34, p = 0.05), hs-CRP (r = 0.36, p = 0.03), and ferritin (r = 0.07, p = 0.001), while being inversely correlated with Total iron binding capacity (TIBC) (r = -0.50, p = 0.003), hemoglobin (r = -0.52, p = 0.001), and glomerular filtration rate (GFR) (r = -0.71, p = 0.000). Serum hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency (55.16 vs. 49 vs. 11.8, p = 0.005). Amongst those with no iron deficiency, hepcidin correlated negatively with hemoglobin (r = -0.752, p-value = 0.007) | ||
| 520 | |a CONCLUSION: A positive correlation between hepcidin and other inflammatory biomarkers in non-dialyzed, iron- and EPO-naïve pediatric CKD patients suggests a role of these markers in higher hepcidin production and its contribution to iron-restricted erythropoiesis across the spectrum of CKD. Median hepcidin levels were highest in those with impaired iron trafficking, followed by those with no iron deficiency, followed by those with absolute iron deficiency, suggesting that in an iron-replete state, high hepcidin levels inhibit iron absorption from the gut and release from iron storing cells, thus restricting erythropoiesis leading to anemia. | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Hepcidins |2 NLM | |
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| 700 | 1 | |a Sahi, Puneet Kaur |e verfasserin |4 aut | |
| 700 | 1 | |a Kaur, Manpreet |e verfasserin |4 aut | |
| 700 | 1 | |a Dubey, Nand Kishore |e verfasserin |4 aut | |
| 700 | 1 | |a Goyal, Parul |e verfasserin |4 aut | |
| 700 | 1 | |a Upadhayay, Ashish Dutt |e verfasserin |4 aut | |
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