Effects of High Iron Levels on Kidney Function
High iron levels can significantly damage kidney function through multiple mechanisms including oxidative stress, inflammation, and direct cellular toxicity, potentially leading to increased morbidity and mortality in patients with kidney disease. 1
Pathophysiological Mechanisms of Iron-Induced Kidney Injury
Iron overload can cause kidney cell damage through ferroptosis, a specialized form of cell death characterized by iron-dependent lipid peroxidation, as demonstrated by upregulation of ferroptosis markers like ferritin light chain (FTL) and prostaglandin-endoperoxide synthase 2 (PTGS2) 2
Excess iron disrupts cellular homeostasis by intensifying oxidative stress and inflammation, leading to disruption of iron-regulating hormones that can accelerate kidney damage 1
Intravenous iron administration can cause acute kidney injury through direct toxic effects, as evidenced by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and inflammatory cytokine excretion 3
High iron levels increase the production of reactive oxygen species in kidney tissue, leading to lipid peroxidation and protein oxidation that damages renal tubular cells 2, 3
Clinical Impact on Kidney Function
In dialysis patients, iron overload can silently increase the burden of complications rather than inducing a full clinical picture, acting as a predictor of iron-mediated oxidative stress and inflammation 1
High ferritin levels (consistently above 100 µg/L) in hemodialysis patients are associated with increased risk of acute cardiocerebrovascular disease (HR: 2.22), infections (HR: 1.76), and death (HR: 2.28) 1
Renal tubules are exposed to high concentrations of iron due to increased glomerular filtration of iron and iron-containing proteins (hemoglobin, transferrin, NGAL) in kidney disease, exacerbating injury 4
Mitochondrial dysfunction in kidney cells occurs with iron overload, with studies showing that iron restriction can restore mitochondrial respiration and respiratory complex activity in diabetic kidney disease 5
Risk Factors and Vulnerable Populations
Dialysis patients with functional iron deficiency are more prone to iatrogenic iron overload than those with true iron deficiency 1
Diabetic dialysis patients (approximately 40% of all dialysis patients) may have a higher risk of complications from iron overload, as even slight increases in iron stores can worsen macrovascular and microvascular complications 1
Patients with pre-existing liver diseases (viral hepatitis B and C, non-alcoholic steatohepatitis) may experience worsening of their condition with iron accumulation 1
Young dialysis patients with repeated graft failure and long cumulative dialysis vintage are at particular risk for long-term exposure to excessive iron 1
Monitoring and Management Considerations
Different IV iron formulations have varying potential to cause adverse effects, with iron gluconate > iron sucrose > iron dextran in terms of capacity to saturate transferrin directly 6, 3
High-dose IV iron (>200 mg/month) in hemodialysis patients is associated with increased risk of acute cardiocerebrovascular disease (HR: 6.02), hospitalization (HR: 2.77), and infections (HR: 5.22) 1
Monitoring ferritin levels is crucial, as a category switch from low to high ferritin is associated with increased risk of acute cardiocerebrovascular disease (HR: 1.59) and death (HR: 6.18) 1
In cases of severe iron overload, chelation therapy with deferasirox may be considered, though it should be used cautiously in patients with kidney impairment 1, 7
Hemodialysis can be effective for removing iron in cases of acute iron toxicity 8
Prevention Strategies
Limiting IV iron doses to less than 136 mg/month may reduce mortality and cardiovascular events in hemodialysis patients 1
Maintenance iron therapy at 200 mg/month is not associated with increased short-term risk of infections, unlike bolus monthly doses of 700 mg 1
Regular monitoring of iron parameters, including ferritin and transferrin saturation, is essential to prevent iron overload in patients receiving iron supplementation 9
In patients with kidney disease, consider iron restriction strategies to improve mitochondrial function and reduce oxidative stress, particularly in diabetic kidney disease 5