Labile plasma iron levels in chronic hemodialysis patients treated by intravenous iron supplementation

Abstract

The increased usage of intravenous iron in hemodialysis patients during recent years has led to increasing concern over the potential development of iron overload. Current methods for detecting iron overload, transferrin saturation, and serum ferritin are neither sensitive nor specific. Labile plasma iron (LPI) represents a component of nontransferrin‐bound iron and may be a more accurate indicator of impending iron overload. We studied whether LPI measured can serve as an early indicator of impending iron overload and mortality in hemodialysis patients. Chronic hemodialysis patients from two medical centers in Israel and Poland who received intravenous iron were included. Baseline clinical and laboratory parameters were recorded. LPI was measured before and 48 hours after a single IV administration. Correlation of positive LPI with laboratory parameters and 2‐year mortality was evaluated. One hundred and one hemodialysis patients were included in the study. LPI became positive post‐administration in 18 (17.8%) patients. Ferritin levels >526 ng/mL and monthly iron doses >250 mg were associated with positive LPI after intravenous iron. At a 2‐year follow‐up, higher mortality was observed in the positive LPI group (61.1% compared to 25.3%, P ≤ .05), although this effect was not statistically significant after multivariate adjustment. A substantial number of hemodialysis patients have positive LPI after intravenous iron administration. LPI positively correlates with laboratory parameters that are currently in routine clinical use for detecting iron overload and with higher intravenous iron dose. Further studies should be conducted to establish the clinical implications of LPI monitoring in hemodialysis patients.

Biomarkers of iron metabolism in chronic kidney disease

“…CKD patients tend to have subclinical inflammatory-related immune activation. The pathogenesis of chronic inflammation in CKD is still not fully understood, yet the proposed underlying factors include oxidative stress, cellular senescence, hypoxia, exogenous factors (such as dialyzer membrane or central venous catheter), immune dysfunction, gut dysbiosis and retention of uremic toxins [100]. Inflammatory blockade is associated with resistance to erythropoietin despite iron availability, which is more clearly understood now that the role of hepcidin in iron metabolism has been identified.…”

Iron homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron‐deficient heart failure

“…Bolus administration of intravenous iron causes marked and rapid increases in circulating iron, which typically exceeds the capacity for transferrin binding, thus causing a remarkable increase in unbound circulating iron, 6,106,107 which has adverse prognostic significance. 108 The uptake of hypersaturated holotransferrin may be toxic to proximal tubular cells, 53 and the abrupt increase in levels of Fe 3+ in the tubular fluid (bound or unbound to transferrin) overwhelms intracellular iron homeostatic mechanisms, leading to an excess of cytosolic labile Fe 2+ , with the potential to trigger ferroptosis. 23,109,110 increases in circulating indicators of lipid peroxidation (malondialdehyde and esterified F2-isoprostanes), along with augmentation of markers of renal injury and inflammation, in proportion to the circulating levels of iron.…”

Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference

“…70,71 The level of labile plasma iron, a component of non-transferrin-bound iron, may also be indicative of impending, clinically significant iron overload. 74 However, validated non-transferrinbound iron and labile plasma iron assays are not widely available, and would require assay standardization, consensus on results reporting, and clinical outcome studies to determine clinically relevant assay formats and toxic thresholds before introduction into clinical practice. 75,76 In addition, data in hereditary hemochromatosis patients suggest that organ damage requires long-term exposure to high TSAT and labile plasma iron levels.…”