A novel diagnostic approach to differentiate iron overload from inflammation in children using transferrin saturation (TSAT) and ferritin-based indices: A cross-sectional study

Gonzales G.F.; Aguilar J.; Yucra S.; Vásquez-Velásquez C. · Science Progress (2025) · DOI: 10.1177/00368504251385071

Resumen

Objective: To evaluate the TSAT*SF and SF/TSAT indices in children living at different altitudes, with and without inflammation, and to examine their correlations with markers of iron homeostasis. Methods: A cross-sectional, multicenter study included 238 children aged 6 to 72 months. We assessed TSAT*SF and SF/TSAT indices in relation to serum hepcidin, total body iron (TBI), hematological and nutritional parameters, and inflammatory markers. Results: Children with elevated inflammatory markers resided at high altitude (HA) and exhibited increased hemoglobin (Hb), hematocrit, and a higher prevalence of erythrocytosis, alongside lower rates of anemia. Log-transformed values of SF, TBI, hepcidin, SF/TSAT ratio, and log(SF/TSAT) were significantly elevated in the inflammation group. In contrast, TSAT*SF values were unaffected by inflammation, showing no significant differences between groups. Among children with normal C-reactive protein (CRP ≤10 mg/L), TSAT*SF > 900 was associated with higher Hb, serum iron, hepcidin, TBI, and TSAT, as well as reduced height-for-age and weight-for-age Z-scores. Across the full sample, CRP positively correlated with ferritin, hepcidin, TBI, neutrophils, and unadjusted Hb, and negatively with serum iron and lymphocytes. CRP showed no correlation with TSAT*SF but was positively associated with the SF/TSAT ratio. Multivariate analysis revealed that the TSAT*SF index correlated with iron status but not inflammation, whereas the SF/TSAT index correlated with both iron status and inflammation. The SF*TSAT ratio demonstrated differential performance, showing a higher area under the ROC curve for the diagnosis of iron deficiency compared to inflammation (0.75 vs 0.98, p <  0.05), whereas the log-transformed SF/TSAT ratio did not exhibit this distinction. Conclusion: The TSAT*SF index effectively identifies tissue iron overload independently of inflammation. Its use may improve iron status assessment in pediatric populations exposed to HA and systemic inflammation. Elevated TSAT*SF was linked to erythrocytosis and impaired growth, underscoring its diagnostic and public health significance. © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Instituciones: Universidad San Ignacio de Loyola; Universidad Católica de Santa María; Universidad Nacional Jorge Basadre Grohmann