Lipocalin-2, Soluble Transferrin Receptor, and Erythropoietin in Anemia During Mild Renal Dysfunction

Abstract

Background Mild renal dysfunction (MRD) is a common condition often associated with diabetes or inflammation and regarded as a risk factor for cardiovascular disease in patients with hypertension. Few studies have examined the role of lipocalin-2 (LCN2) as a regulator of iron and a contributor to anemia in MRD. The aim of this study was to investigate the relationship between LCN2, soluble transferrin receptor (sTfR), erythropoietin (EPO), reticulocyte production, and the prevalence of anemia in MRD. Methods A total of 235 subjects with MRD were evaluated. LCN2, sTfR, EPO, and iron levels were measured. Reticulocyte maturity index (RMI) and corrected LCN2 (cLCN2) values were calculated using reticulocyte subpopulations and the inflammation index, respectively. Results Subjects with LCN2 elevation had significantly higher sTfR and significantly lower RMI levels than those without LCN2 elevation. Compared to subjects without LCN2 elevation, those with LCN2 elevation exhibited significantly lower hemoglobin (12.9 ± 1.6 g/dL vs 14.0 ± 1.7 g/dL, p < 0.001) and more prevalent anemia (27.7% vs 13.3%, p = 0.008). Patients with anemia had significantly higher LCN2 and cLCN2 than those without anemia. LCN2 was positively correlated with sTfR and negatively correlated with RMI but not EPO. Elevated LCN2 led to a 1.3-fold increase in the prevalence of anemia (odds ratio: 1.302; 95% CI: 1.012–2.527; p < 0.001). Conclusion LCN2 elevation may contribute to the development of anemia in MRD, particularly in conjunction with restricted iron availability and suppressed reticulocyte production.

Anemia of Chronic Kidney Disease—A Narrative Review of Its Pathophysiology, Diagnosis, and Management

“…Soluble transferrin receptor (sTfR) is an extracellular portion of membranous glycoprotein contributing to iron transport through the cellular membrane and is present on most of the cells, especially in requiring high amounts of iron [ 91 , 92 ]. Several studies have confirmed the utility of sTfR to assess iron status, indicating comparable ability in diagnosing iron deficiency anemia to ferritin; however, it is not influenced by inflammation [ 92 ].…”

Lipocalin-2: A Nurturer of Tumor Progression and a Novel Candidate for Targeted Cancer Therapy

“…In this context, tumor cells can produce cytokines that negatively affect erythroid progenitor cell differentiation. Moreover, Lcn-2 has been shown to also affect erythropoiesis negatively, and this is related to the occurrence of hypoxic TAMs and the development of metastasis [34][35][36]. Hence, Lcn-2, through its iron-regulating role, could be implicated as a pivotal player in CRA by regulating the inflammatory immune response within the TME and iron availability for erythropoiesis [37][38][39].…”