# Functional iron deficiency and outcomes in patients with kidney disease

**Authors:** Hannah O’Keeffe, Firas AlTheyaib, Isabelle Newman, Sharmilee Rengarajan, Samira Lakhal-Littleton, Ivona Baricevic-Jones, Rajkumar Chinnadurai, Philip A. Kalra, Ken Iseri, Ken Iseri, Ken Iseri

PMC · DOI: 10.1371/journal.pone.0343724 · PLOS One · 2026-03-24

## TL;DR

This study shows that functional iron deficiency increases mortality and hospitalization risks in patients with kidney disease.

## Contribution

The study identifies functional iron deficiency as an independent risk factor for mortality in kidney disease patients.

## Key findings

- FID was independently associated with all-cause mortality in both HD and CKD patients.
- FID patients on HD had higher hospitalization rates and longer hospital stays.
- Mortality rates were highest in FID patients compared to those with no or absolute iron deficiency.

## Abstract

This study assesses the impact of functional iron deficiency (FID) on outcomes, including all-cause mortality, hospitalizations and non-fatal cardiovascular events in patients with non-dialysis chronic kidney disease (CKD) and hemodialysis (HD).

In HD, absolute iron deficiency (AID) was defined as ferritin < 200 µg/L and TSAT (transferrin saturation) ≤ 20%, and FID ferritin ≥200 µg/L with TSAT ≤20%. In CKD, AID was ferritin < 100 µg/L and TSAT ≤ 20%, and FID ferritin ≥ 100 µg/L with TSAT ≤ 20%. Prevalent HD patients as of January 2012 and incident patients between January 2012 and December 2014 were included (n = 512) and followed to 31/12/2018 (median 36.5 months). CKD patients who received iron infusions between January 2017 and December 2019 were included (n = 831) and followed until 31/12/2023 (median 38.5 months).

In the HD cohort, 71% of the FID patients were dead at the end of follow-up (vs No Iron Deficiency, NID: 52%, AID: 48%; p = 0.008). In the CKD cohort, 62% of the FID group died by the end of follow-up (vs AID: 49.5%, NID: 46.2%; p = 0.001). The hazard ratio for FID for all-cause mortality was 1.89 (p < 0.001) in HD and 1.48 (p < 0.001) in CKD. Multivariate analysis found FID was independently associated with all-cause mortality (HD HR:1.50, p = 0.015; CKD HR: 1.46, p = 0.017). Patients with FID on HD were more likely to be hospitalized (median episodes 2.5 FID vs 2 in AID and NID, p = 0.041; FID: 22.5 days vs AID: 10, NID:14 days, p = 0.019).

FID was associated with all-cause mortality in patients with non-dialysis CKD and HD, and with higher rates of hospitalization and prolonged length of stay in HD.

## Linked entities

- **Diseases:** chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, HAMP (hepcidin antimicrobial peptide) [NCBI Gene 57817] {aka HEPC, HFE2B, LEAP1, PLTR}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** Anemia (MESH:D000740), hypercholesterolemia (MESH:D006937), blood loss (MESH:D016063), cardiovascular disease (MESH:D002318), chronic liver disease (MESH:D008107), congestive cardiac failure (MESH:D006333), hypertension (MESH:D006973), cardiac arrest (MESH:D006323), Chronic inflammation (MESH:D007249), diabetes (MESH:D003920), erythropoietin deficiency (MESH:D007153), COPD (MESH:D029424), gastrointestinal disorders (MESH:D005767), FID (MESH:D000090463), CCF (MESH:D003025), CKD (MESH:D051436), ischemic heart disease (MESH:D017202), peripheral vascular disease (MESH:D016491), CVA (MESH:D020521), myocardial infarction (MESH:D009203), DM (MESH:D009223), NID (MESH:C537394), kidney disease (MESH:D007674), died (MESH:D003643), ESA (MESH:D007037), ACADEMIC EDITOR (MESH:D007859), cancer (MESH:D009369), CV disease (MESH:D004194), iron-restricted erythropoiesis (MESH:D002313)
- **Chemicals:** carbohydrate (MESH:D002241), Iron (MESH:D007501), Calcium- 10 (-), phosphate (MESH:D010710)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13012524/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC13012524/full.md

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Source: https://tomesphere.com/paper/PMC13012524