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Erythropoiesis-independent effects of iron in chronic kidney disease

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Abstract

Chronic kidney disease (CKD) leads to alterations of iron metabolism, which contribute to the development of anemia and necessitates iron supplementation in patients with CKD. Elevated hepcidin accounts for a significant iron redistribution in CKD. Recent data indicate that these alterations in iron homeostasis coupled with therapeutic iron supplementation have pleiotropic effects on many organ systems in patients with CKD, far beyond the traditional hematologic effects of iron; these include effects of iron on inflammation, oxidative stress, kidney fibrosis, cardiovascular disease, CKD-mineral and bone disorder, and skeletal growth in children. The effects of iron supplementation appear to be largely dependent on the route of administration and on the specific iron preparation. Iron-based phosphate binders exemplify the opportunity for using iron for both traditional (anemia) and novel (hyperphosphatemia) indications. Further optimization of iron therapy in patients with CKD may inform new approaches to the treatment of CKD complications and potentially allow modification of disease progression.

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References

  1. Akchurin M, Schneider MF, Mulqueen L, Brooks ER et al (2014) Medication adherence and growth in children with CKD. Clin J Am Soc Nephrol 9:1519–1525

    Article  PubMed  PubMed Central  Google Scholar 

  2. Fishbane S, Pollack S, Feldman HI, Joffe MM (2009) Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988–2004. Clin J Am Soc Nephrol 4:57–61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rosenblatt SG, Drake S, Fadem S, Welch R et al (1982) Gastrointestinal blood loss in patients with chronic renal failure. Am J Kidney Dis 1:232–236

    Article  CAS  PubMed  Google Scholar 

  4. Chen W, Ducharme-Smith K, Davis L, Hui WF et al (2017) Dietary sources of energy and nutrient intake among children and adolescents with chronic kidney disease. Pediatr Nephrol 32:1233–1241

    Article  PubMed  PubMed Central  Google Scholar 

  5. Atkinson MA, Pierce CB, Fadrowski JJ, Benador NM et al (2012) Association between common iron store markers and hemoglobin in children with chronic kidney disease. Pediatr Nephrol 27:2275–2283

    Article  PubMed  PubMed Central  Google Scholar 

  6. Atkinson MA, Kim JY, Roy CN, Warady BA et al (2015) Hepcidin and risk of anemia in CKD: a cross-sectional and longitudinal analysis in the CKiD cohort. Pediatr Nephrol 30:635–643

    Article  PubMed  Google Scholar 

  7. Akchurin O, Sureshbabu A, Doty SB, Zhu Y-S et al (2016) Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease. Am J Physiol Ren Physiol 311:F877–F889

    Article  CAS  Google Scholar 

  8. Akchurin O, Patino E, Dalal V, Meza K et al (2019) Interleukin-6 contributes to the development of anemia in juvenile CKD. Kidney Int Rep 4:470–483

    Article  PubMed  Google Scholar 

  9. Hamano H, Ikeda Y, Watanabe H, Horinouchi Y et al (2018) The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease. Nephrol Dial Transplant 33:586–597

    Article  CAS  PubMed  Google Scholar 

  10. Yamamoto K, Kuragano T, Kimura T, Nanami M et al (2018) Interplay of adipocyte and hepatocyte: Leptin upregulates hepcidin. Biochem Biophys Res Commun 495:1548–1554

    Article  CAS  PubMed  Google Scholar 

  11. Brasse-Lagnel C, Karim Z, Letteron P, Bekri S et al (2011) Intestinal DMT1 cotransporter is down-regulated by hepcidin via proteasome internalization and degradation. Gastroenterology 140:1261–1271.e1261

    Article  CAS  PubMed  Google Scholar 

  12. Renders L, Budde K, Rosenberger C, van Swelm R et al (2019) First-in-human Phase I studies of PRS-080# 22, a hepcidin antagonist, in healthy volunteers and patients with chronic kidney disease undergoing hemodialysis. PLoS One 14:e0212023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Patino E, Doty SB, Bhatia D, Meza K et al (2020) Carbonyl iron and iron dextran therapies cause adverse effects on bone health in juveniles with chronic kidney disease. Kidney Int 98:1210–1224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Provenzano R, Besarab A, Sun CH, Diamond SA et al (2016) Oral hypoxia–inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment of anemia in patients with CKD. Clin J Am Soc Nephrol 11:982–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kular D, Macdougall IC (2019) HIF stabilizers in the management of renal anemia: from bench to bedside to pediatrics. Pediatr Nephrol 34:365–378

    Article  PubMed  Google Scholar 

  16. Meza K, Biswas S, Zhu Y-S, Gajjar A et al (2021) Tumor necrosis factor-alpha is associated with mineral bone disorder and growth impairment in children with chronic kidney disease. Pediatr Nephrol 36:1579–1587

    Article  PubMed  Google Scholar 

  17. Lim CS, Vaziri ND (2004) The effects of iron dextran on the oxidative stress in cardiovascular tissues of rats with chronic renal failure. Kidney Int 65:1802–1809

    Article  CAS  PubMed  Google Scholar 

  18. Agarwal R (2008) Iron, oxidative stress, and clinical outcomes. Pediatr Nephrol 23:1195–1199

    Article  PubMed  Google Scholar 

  19. Sonnweber T, Theurl I, Seifert M, Schroll A et al (2011) Impact of iron treatment on immune effector function and cellular iron status of circulating monocytes in dialysis patients. Nephrol Dial Transplant 26:977–987

    Article  CAS  PubMed  Google Scholar 

  20. Ganz T, Bino A, Salusky IB (2019) Mechanism of action and clinical attributes of Auryxia® (ferric citrate). Drugs 79:957–968

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lau WL, Vaziri ND, Nunes AC, Comeau AM et al (2018) The phosphate binder ferric citrate alters the gut microbiome in rats with chronic kidney disease. J Pharmacol Exp Ther 367:452–460

    Article  CAS  PubMed  Google Scholar 

  22. Tanaka M, Miyamura S, Imafuku T, Tominaga Y et al (2016) Effect of a ferric citrate formulation, a phosphate binder, on oxidative stress in chronic kidney diseases-mineral and bone disorder patients receiving hemodialysis: a pilot study. Biol Pharm Bull 39:1000–1006

    Article  CAS  PubMed  Google Scholar 

  23. Jing W, Nunes AC, Farzaneh T, Khazaeli M et al (2018) Phosphate binder, ferric citrate, attenuates anemia, renal dysfunction, oxidative stress, inflammation, and fibrosis in 5/6 nephrectomized CKD rats. J Pharmacol Exp Ther 367:129–137

    Article  CAS  PubMed  Google Scholar 

  24. Umanath K, Jalal DI, Greco BA, Umeukeje EM et al (2015) Ferric citrate reduces intravenous iron and erythropoiesis-stimulating agent use in ESRD. J Am Soc Nephrol 26:2578–2587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stefanova D, Raychev A, Deville J, Humphries R et al (2018) Hepcidin protects against lethal Escherichia coli sepsis in mice inoculated with isolates from septic patients. Infect Immun 86:e00253–e00318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Patruta S, Edlinger R, Sunder-Plassmann G, Hörl W (1998) Neutrophil impairment associated with iron therapy in hemodialysis patients with functional iron deficiency. J Am Soc Nephrol 9:655–663

    Article  CAS  PubMed  Google Scholar 

  27. Otaki Y, Nakanishi T, Hasuike Y, Moriguchi R et al (2004) Defective regulation of iron transporters leading to iron excess in the polymorphonuclear leukocytes of patients on maintenance hemodialysis. Am J Kidney Dis 43:1030–1039

    Article  CAS  PubMed  Google Scholar 

  28. Moriguchi R, Otaki Y, Hazeki S, Shimada T et al (2012) High levels of tumor necrosis factor-α downregulate antimicrobial iron transport protein, Nramp1, in chronic hemodialysis patients: a key factor for infection risk. Am J Nephrol 35:372–378

    Article  CAS  PubMed  Google Scholar 

  29. Kuo K-L, Hung S-C, Wei Y-H, Tarng D-C (2008) Intravenous iron exacerbates oxidative DNA damage in peripheral blood lymphocytes in chronic hemodialysis patients. J Am Soc Nephrol 19:1817–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ducloux D, Legendre M, Bamoulid J, Rebibou J-M et al (2018) ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications. Immun Ageing 15:16

    Article  PubMed  PubMed Central  Google Scholar 

  31. Walker EM, Walker SM (2000) Effects of iron overload on the immune system. Ann Clin Lab Sci 30:354–365

    CAS  PubMed  Google Scholar 

  32. Liu JH, Liu YL, Lin HH, Yang YF et al (2009) Intravenous iron attenuates postvaccination anti-HBsAg titres after quadruple hepatitis B vaccination in dialysis patients with erythropoietin therapy. Int J Clin Pract 63:387–393

    Article  CAS  PubMed  Google Scholar 

  33. Recalcati S, Locati M, Marini A, Santambrogio P et al (2010) Differential regulation of iron homeostasis during human macrophage polarized activation. Eur J Immunol 40:824–835

    Article  CAS  PubMed  Google Scholar 

  34. Brookhart MA, Freburger JK, Ellis AR, Wang L et al (2013) Infection risk with bolus versus maintenance iron supplementation in hemodialysis patients. J Am Soc Nephrol 24:1151–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Tangri N, Miskulin DC, Zhou J, Bandeen-Roche K et al (2015) Effect of intravenous iron use on hospitalizations in patients undergoing hemodialysis: a comparative effectiveness analysis from the DEcIDE-ESRD study. Nephrol Dial Transplant 30:667–675

    Article  CAS  PubMed  Google Scholar 

  36. Kuragano T, Matsumura O, Matsuda A, Hara T et al (2014) Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Kidney Int 86:845–854

    Article  CAS  PubMed  Google Scholar 

  37. Agarwal R, Kusek JW, Pappas MK (2015) A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int 88:905–914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Qunibi WY, Martinez C, Smith M, Benjamin J et al (2011) A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients. Nephrol Dial Transplant 26:1599–1607

    Article  CAS  PubMed  Google Scholar 

  39. Roger SD, Gaillard CA, Bock AH, Carrera F et al (2017) Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial. Nephrol Dial Transplant 32:1530–1539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Macdougall IC, White C, Anker SD, Bhandari S et al (2019) Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med 380:447–458

    Article  CAS  PubMed  Google Scholar 

  41. van Raaij SE, Rennings AJ, Biemond BJ, Schols SE et al (2019) Iron handling by the human kidney: glomerular filtration and tubular reabsorption both contribute to urinary iron excretion. Am J Physiol Ren Physiol 316:F606–F614

    Article  Google Scholar 

  42. Norden AG, Lapsley M, Lee PJ, Pusey CD et al (2001) Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int 60:1885–1892

    Article  CAS  PubMed  Google Scholar 

  43. Green R, Charlton R, Seftel H, Bothwell T et al (1968) Body iron excretion in man: a collaborative study. Am J Med 45:336–353

    Article  CAS  PubMed  Google Scholar 

  44. Wareing M, Ferguson CJ, Green R, Riccardi D et al (2000) In vivo characterization of renal iron transport in the anaesthetized rat. J Physiol 524:581–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wareing M, Ferguson CJ, Delannoy M, Cox AG et al (2003) Altered dietary iron intake is a strong modulator of renal DMT1 expression. Am J Physiol Ren Physiol 285:F1050–F1059

    Article  CAS  Google Scholar 

  46. Wolff NA, Liu W, Fenton RA, Lee WK et al (2011) Ferroportin 1 is expressed basolaterally in rat kidney proximal tubule cells and iron excess increases its membrane trafficking. J Cell Mol Med 15:209–219

    Article  CAS  PubMed  Google Scholar 

  47. Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C et al (2001) Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci U S A 98:12491–12496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Scindia Y, Leeds J, Swaminathan S (2019) Iron homeostasis in healthy kidney and its role in acute kidney injury. Semin Nephrol 39:76–84

    Article  CAS  Google Scholar 

  49. Wang X, Zheng X, Zhang J, Zhao S et al (2018) Physiological functions of ferroportin in the regulation of renal iron recycling and ischemic acute kidney injury. Am J Physiol Ren Physiol 315:F1042–F1057

    Article  CAS  Google Scholar 

  50. Mohammad G, Matakidou A, Robbins PA, Lakhal-Littleton S (2021) The kidney hepcidin/ferroportin axis controls iron reabsorption and determines the magnitude of kidney and systemic iron overload. Kidney Int. https://doi.org/10.1016/j.kint.2021.04.034

  51. Pan S, Qian Z-M, Cui S, Zhao D et al (2020) Local hepcidin increased intracellular iron overload via the degradation of ferroportin in the kidney. Biochem Biophys Res Commun 522:322–327

    Article  CAS  PubMed  Google Scholar 

  52. Mleczko-Sanecka K, Silvestri L (2021) Cell-type-specific insights into iron regulatory processes. Am J Hematol 96:110–127

    Article  CAS  PubMed  Google Scholar 

  53. van Swelm RP, Wetzels JF, Verweij VG, Laarakkers CM et al (2016) Renal handling of circulating and renal-synthesized hepcidin and its protective effects against hemoglobin–mediated kidney injury. J Am Soc Nephrol 27:2720–2732

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ludwiczek S, Theurl I, Muckenthaler MU, Jakab M et al (2007) Ca 2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med 13:448–454

    Article  CAS  PubMed  Google Scholar 

  55. Ferguson CJ, Wareing M, Delannoy M, Fenton R et al (2003) Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade (b) rat. Kidney Int 64:1755–1764

    Article  CAS  PubMed  Google Scholar 

  56. Ikeda Y, Enomoto H, Tajima S, Izawa-Ishizawa Y et al (2013) Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice. Am J Physiol Ren Physiol 304:F1028–F1036

    Article  CAS  Google Scholar 

  57. Prinsen BH, De Sain-Van Der MG, Kaysen GA, Straver HW et al (2001) Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses. J Am Soc Nephrol 12:1017–1025

    Article  CAS  PubMed  Google Scholar 

  58. Nakatani S, Nakatani A, Ishimura E, Toi N et al (2018) Urinary iron excretion is associated with urinary full-length megalin and renal oxidative stress in chronic kidney disease. Kidney Blood Press Res 43:458–470

    Article  CAS  PubMed  Google Scholar 

  59. Naito Y, Fujii A, Sawada H, Oboshi M et al (2015) Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease. Hypertens Res 38:463–470

    Article  CAS  PubMed  Google Scholar 

  60. Nankivell BJ, Boadle RA, Harris DC (1992) Iron accumulation in human chronic renal disease. Am J Kidney Dis 20:580–584

    Article  CAS  PubMed  Google Scholar 

  61. Peña-Montes DJ, Huerta-Cervantes M, Ríos-Silva M, Trujillo X et al (2020) Effects of dietary iron restriction on kidney mitochondria function and oxidative stress in streptozotocin-diabetic rats. Mitochondrion 54:41–48

    Article  PubMed  Google Scholar 

  62. Remuzzi A, Puntorieri S, Brugnetti B, Bertani T et al (1991) Renoprotective effect of low iron diet and its consequence on glomerular hemodynamics. Kidney Int 39:647–652

    Article  CAS  PubMed  Google Scholar 

  63. Ikeda Y, Ozono I, Tajima S, Imao M et al (2014) Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction. PLoS One 9:e89355

    Article  PubMed  PubMed Central  Google Scholar 

  64. Chaudhary K, Chilakala A, Ananth S, Mandala A et al (2019) Renal iron accelerates the progression of diabetic nephropathy in the HFE gene knockout mouse model of iron overload. Am J Physiol Ren Physiol 317:F512–F517

    Article  CAS  Google Scholar 

  65. Francis C, Courbon G, Gerber C, Neuburg S et al (2019) Ferric citrate reduces fibroblast growth factor 23 levels and improves renal and cardiac function in a mouse model of chronic kidney disease. Kidney Int 96:1346–1358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Neven E, Corremans R, Vervaet BA, Funk F et al (2020) Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure. Nephrol Dial Transplant 35:1689–1699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bolisetty S, Zarjou A, Hull TD, Traylor AM et al (2015) Macrophage and epithelial cell H-ferritin expression regulates renal inflammation. Kidney Int 88:95–108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Balogh E, Tolnai E, Nagy B Jr, Nagy B et al (2016) Iron overload inhibits osteogenic commitment and differentiation of mesenchymal stem cells via the induction of ferritin. Biochim Biophys Acta 1862:1640–1649

    Article  CAS  PubMed  Google Scholar 

  69. Kim BJ, Ahn SH, Bae SJ, Kim EH et al (2012) Iron overload accelerates bone loss in healthy postmenopausal women and middle-aged men: a 3-year retrospective longitudinal study. J Bone Miner Res 27:2279–2290

    Article  CAS  PubMed  Google Scholar 

  70. Wang X, Chen B, Sun J, Jiang Y et al (2018) Iron-induced oxidative stress stimulates osteoclast differentiation via NF-κB signaling pathway in mouse model. Metabolism 83:167–176

    Article  CAS  PubMed  Google Scholar 

  71. Fishbane S, Block GA, Loram L, Neylan J et al (2017) Effects of ferric citrate in patients with nondialysis-dependent CKD and iron deficiency anemia. J Am Soc Nephrol 28:1851–1858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Block GA, Block MS, Smits G, Mehta R et al (2019) A pilot randomized trial of ferric citrate coordination complex for the treatment of advanced CKD. J Am Soc Nephrol 30:1495–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Womack R, Berru F, Panwar B, Gutiérrez OM (2020) Effect of ferric citrate versus ferrous sulfate on iron and phosphate parameters in patients with iron deficiency and CKD: a randomized trial. Clin J Am Soc Nephrol 15:1251–1258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Abu-Zaid A, Magzoub D, Aldehami MA, Behiry AA et al (2021) The effect of iron supplementation on FGF23 in chronic kidney disease patients: a systematic review and time-response meta-analysis. Biol Trace Elem Res. https://doi.org/10.1007/s12011-021-02598-1

  75. Hanudel MR, Chua K, Rappaport M, Gabayan V et al (2016) Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice. Am J Physiol Ren Physiol 311:F1369–F1377

    Article  Google Scholar 

  76. Honda H, Michihata T, Shishido K, Takahashi K et al (2017) High fibroblast growth factor 23 levels are associated with decreased ferritin levels and increased intravenous iron doses in hemodialysis patients. PLoS One 12:e0176984

    Article  PubMed  PubMed Central  Google Scholar 

  77. David V, Martin A, Isakova T, Spaulding C et al (2016) Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production. Kidney Int 89:135–146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Clinkenbeard EL, Noonan ML, Thomas JC, Ni P et al (2019) Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD. JCI Insight 4:e123817

    Article  PubMed Central  Google Scholar 

  79. Shalhoub V, Shatzen EM, Ward SC, Davis J et al (2012) FGF23 neutralization improves chronic kidney disease–associated hyperparathyroidism yet increases mortality. J Clin Invest 122:2543–2553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Mandalunis PM, Ubios AM (2005) Experimental renal failure and iron overload: a histomorphometric study in rat tibia. Toxicol Pathol 33:398–403

    Article  CAS  PubMed  Google Scholar 

  81. Iida A, Kemmochi Y, Kakimoto K, Tanimoto M et al (2013) Ferric citrate hydrate, a new phosphate binder, prevents the complications of secondary hyperparathyroidism and vascular calcification. Am J Nephrol 37:346–358

    Article  CAS  PubMed  Google Scholar 

  82. Akchurin M (2019) Chronic kidney disease and dietary measures to improve outcomes. Pediatr Clin N Am 66:247–267

    Article  Google Scholar 

  83. Soliman AT, Al Dabbagh MM, Habboub AH, Adel A et al (2009) Linear growth in children with iron deficiency anemia before and after treatment. J Trop Pediatr 55:324–327

    Article  PubMed  Google Scholar 

  84. Rodig NM, McDermott KC, Schneider MF, Hotchkiss HM et al (2014) Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study. Pediatr Nephrol 29:1987–1995

    Article  PubMed  PubMed Central  Google Scholar 

  85. Seikaly MG, Salhab N, Gipson D, Yiu V et al (2006) Stature in children with chronic kidney disease: analysis of NAPRTCS database. Pediatr Nephrol 21:793

    Article  PubMed  Google Scholar 

  86. Behnisch R, Kirchner M, Anarat A, Bacchetta J et al (2019) Determinants of statural growth in European children with chronic kidney disease: findings from the Cardiovascular Comorbidity in Children With Chronic Kidney Disease (4C) Study. Front Pediatr 7:278

    Article  PubMed  PubMed Central  Google Scholar 

  87. Skordis N, Kyriakou A (2011) The multifactorial origin of growth failure in thalassaemia. Pediatr Endocrinol Rev 8(Suppl 2):271–277

    PubMed  Google Scholar 

  88. Sachdev H, Gera T, Nestel P (2006) Effect of iron supplementation on physical growth in children: systematic review of randomised controlled trials. Public Health Nutr 9:904–920

    Article  PubMed  Google Scholar 

  89. Perng W, Mora-Plazas M, Marin C, Villamor E (2013) Iron status and linear growth: a prospective study in school-age children. Eur J Clin Nutr 67:646–651

    Article  CAS  PubMed  Google Scholar 

  90. Bhandari S, Allgar V, Lamplugh A, Macdougall IC et al (2020) Protocol and baseline data of a multicentre prospective double-blinded randomized study of intravenous iron on functional status in patients with chronic kidney disease. Am J Nephrol 51:493–500

    Article  CAS  PubMed  Google Scholar 

  91. Matteucci MC, Wühl E, Picca S, Mastrostefano A et al (2006) Left ventricular geometry in children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol 17:218–226

    Article  PubMed  Google Scholar 

  92. Agarwal R, Rizkala AR, Bastani B, Kaskas MO et al (2006) A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol 26:445–454

    Article  CAS  PubMed  Google Scholar 

  93. Reis KA, Guz G, Ozdemir H, Erten Y et al (2005) Intravenous iron therapy as a possible risk factor for atherosclerosis in end-stage renal disease. Int Heart J 46:255–264

    Article  CAS  PubMed  Google Scholar 

  94. Kuragano T, Itoh K, Shimonaka Y, Kida A et al (2011) Hepcidin as well as TNF-α are significant predictors of arterial stiffness in patients on maintenance hemodialysis. Nephrol Dial Transplant 26:2663–2667

    Article  CAS  PubMed  Google Scholar 

  95. Seto T, Hamada C, Tomino Y (2014) Suppressive effects of iron overloading on vascular calcification in uremic rats. J Nephrol 27:135–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zarjou A, Jeney V, Arosio P, Poli M et al (2009) Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells. J Am Soc Nephrol 20:1254–1263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bhandari S, Kalra PA, Berkowitz M, Belo D et al (2021) Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant 36:111–120

    Article  CAS  PubMed  Google Scholar 

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OA is supported by the K08 DK114558 from the NIH NIDDK and by the Rohr Family Clinical Scholar Award from Weill Cornell Medicine.

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Patino, E., Akchurin, O. Erythropoiesis-independent effects of iron in chronic kidney disease. Pediatr Nephrol 37, 777–788 (2022). https://doi.org/10.1007/s00467-021-05191-9

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