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Letter to the Editor
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Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients

Guy Rostoker, Fanny Lepeytre and Jacques Rottembourg
JASN March 2022, 33 (3) 654-655; DOI: https://doi.org/10.1681/ASN.2021081044
Guy Rostoker
1Division of Nephrology and Dialysis, Ramsay Santé, Claude Galien Hospital, Quincy-sous-Sénart, France
2Collège de Médecine des Hôpitaux de Paris, Paris, France
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Fanny Lepeytre
1Division of Nephrology and Dialysis, Ramsay Santé, Claude Galien Hospital, Quincy-sous-Sénart, France
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Jacques Rottembourg
3Division of Nephrology, Dialysis and Transplantation, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
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  • non-dialysis CKD
  • ferritin
  • transferrin saturation
  • mortality
  • cardiovascular events
  • inflammation

In their recently published article in JASN, Guedes et al.1 analyzed data from the Chronic Kidney Disease Outcomes and Practice Patterns Study (comprising 5145 patients from France, Germany, United States, and Brazil, enrolled between 2013 and 2017). They found that, in patients with nondialysis CKD, there was an association between transferrin saturation ≤15% and increased all-cause mortality and major cardiovascular adverse events, regardless of anemia. In addition, transferrin saturation ≥46% and ferritin ≥300 ng/ml tended to be associated with increased all-cause mortality, but these associations were NS. These results are in line with biologic data showing the pivotal role of iron in DNA synthesis and repair2 as an increase in ferroptosis in an iron-overloaded state.3

In addition to being biomarkers widely used by nephrologists to monitor iron storage (ferritin) and iron availability (transferrin and transferrin saturation) in patients with nondialysis and dialysis CKD, ferritin, transferrin, and transferrin saturation are also acute-phase reactants.4 Inflammation is common in patients with nondialysis CKD and is implicated in the pathophysiology of cardiovascular events in both patients with and without renal disease.4

These authors performed survival analyses using Cox proportional hazard models adjusted for various confounders known to influence survival in patients with nondialysis CKD.1 We suggest inclusion of inflammation as a covariate, in addition to the factors in their models, because it is an important confounding factor in the measurement of ferritin and transferrin saturation that is also known to influence mortality and cardiovascular events in patients with nondialysis CKD. Detailed analyses using various biomarkers of inflammation could be informative to fully explore the association between current serum iron biomarkers and mortality, cardiovascular events, or both in patients with nondialysis CKD.

Disclosures

G. Rostoker reports receiving research funding, via scientific presentations, from Amgen, Astellas, Baxter, Hemotech, Hospal-Gambro, Nipro, Physidia France, and Theradial; having consultancy agreements with Astellas France (via the board on roxadustat 2019–2021); serving on speakers bureaus for Astellas and Baxter; and receiving honoraria from Amgen, Astellas, Roche, and Sanofi. All remaining authors have nothing to disclose.

Funding

None.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • See related reply, “Authors’ Reply,” on pages 655–656, and original article, “Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia,” in Vol. 32, Iss. 8, on pages 2020–2030.

  • Copyright © 2022 by the American Society of Nephrology

References

  1. ↵
    1. Guedes M,
    2. Muenz DG,
    3. Zee J,
    4. Bieber B,
    5. Stengel B,
    6. Massy ZA, et al; CKDopps Investigators
    : Serum biomarkers of iron stores are associated with increased risk of all-cause mortality and cardiovascular events in nondialysis CKD patients, with or without anemia. J Am Soc Nephrol 32: 2020–2030, 2021
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Puig S,
    2. Ramos-Alonso L,
    3. Romero AM,
    4. Martínez-Pastor MT
    : The elemental role of iron in DNA synthesis and repair. Metallomics 9: 1483–1500, 2017
    OpenUrlCrossRef
  3. ↵
    1. Stockwell BR,
    2. Friedmann Angeli JP,
    3. Bayir H,
    4. Bush AI,
    5. Conrad M,
    6. Dixon SJ, et al
    : Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171: 273–285, 2017
    OpenUrlCrossRefPubMed
  4. ↵
    1. Wish JB
    : Assessing iron status: Beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol 1: S4–S8, 2006
    OpenUrlAbstract/FREE Full Text
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Journal of the American Society of Nephrology: 33 (3)
Journal of the American Society of Nephrology
Vol. 33, Issue 3
March 2022
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Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients
Guy Rostoker, Fanny Lepeytre, Jacques Rottembourg
JASN Mar 2022, 33 (3) 654-655; DOI: 10.1681/ASN.2021081044

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Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients
Guy Rostoker, Fanny Lepeytre, Jacques Rottembourg
JASN Mar 2022, 33 (3) 654-655; DOI: 10.1681/ASN.2021081044
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  • Authors’ Reply: Kidney Histopathology in ANCA-Associated Vasculitides Treated with Plasma Exchange
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