Inflammation, Serum Iron, and Risk of Mortality and Cardiovascular Events in Nondialysis CKD Patients

• 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.

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