Goyal Kamal Kumar, Saha Abhijeet, Sahi Puneet Kaur, Kaur Manpreet, Dubey Nand Kishore, Goyal Parul, Upadhayay Ashish Dutt
Clin Nephrol. 2018 May;89(5):363-370. doi: 10.5414/CN109132.
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.
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.
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. .
铁调素是铁调素 - 铁转运蛋白轴的主要调节因子，在慢性肾脏病（CKD）儿童中水平升高。在未接受铁剂和促红细胞生成素（EPO）治疗、未进行透析的CKD儿童中，CKD贫血及其与铁调素、白细胞介素 - 6（IL - 6）、肿瘤坏死因子 - α（TNF - α）和高敏C反应蛋白（hs - CRP）的关系研究不足。
本病例对照研究旨在研究未接受铁剂和EPO治疗、未进行透析的CKD（3 - 5期）患者中铁调素及其他促炎标志物（IL - 6、TNF - α、hs - CRP）的水平及其与贫血的关系。将32例年龄在2 - 18岁、未曾接受过铁剂或EPO治疗的儿科CKD 3 - 5期患者与32例年龄和性别匹配的健康对照进行比较。CKD病例还根据其血清铁蛋白水平和转铁蛋白饱和度（%TSAT）分为三类：真性缺铁、铁转运受损和无缺铁。然后将基线铁状态与血清铁调素水平进行关联分析。
与对照组相比，血清铁调素、IL - 6和TNF - α水平显著升高。随着CKD分期进展，血红蛋白水平下降，而血清铁调素、IL - 6、TNF - α和hs - CRP水平显著升高。血清铁调素水平与IL - 6（r = 0.57，p = 0.001）、TNF - α（r = 0.34，p = 0.05）、hs - CRP（r = 0.36，p = 0.03）和铁蛋白（r = 0.07，p = 0.001）呈正相关，而与总铁结合力（TIBC）（r = -0.50，p = 0.003）、血红蛋白（r = -0.52，p = 0.001）和肾小球滤过率（GFR）（r = -0.71，p = 0.000）呈负相关。铁转运受损患者的血清铁调素水平最高，其次是无缺铁患者，绝对缺铁患者最低（55.16 vs. 49 vs. 11.8，p = 0.005）。在无缺铁患者中，铁调素与血红蛋白呈负相关（r = -0.752，p值 = 0.007）。
在未进行透析、未接受铁剂和EPO治疗的儿科CKD患者中，铁调素与其他炎症生物标志物之间的正相关表明这些标志物在铁调素产生增加中起作用，及其在整个CKD范围内对铁限制红细胞生成的影响。铁转运受损患者的铁调素中位数水平最高，其次是无缺铁患者，绝对缺铁患者最低，这表明在铁充足状态下，高铁调素水平会抑制肠道铁吸收和铁储存细胞的铁释放，从而限制红细胞生成导致贫血。
