The Under-Recognised “Falsely-High” Transferrin Saturation Phenotype in Peritoneal Dialysis Patients: Hypotransferrinaemia, Nutrition–Inflammation, and Clinical Implications

Abstract Description

Authors (including presenting author) :

Chan ATP (1), Sin CSR(1), Kwan JTC (1)

Affiliation :

Division of Nephrology, Department of Medicine, North District Hospital.

Keyword 1: :

Peritoneal dialysis

Keyword 2: :

Chronic kidney disease

Keyword 3: :

Iron profile

Keyword 4: :

Malnutrition

Keyword 5: :

Inflammation

Introduction :

In maintenance peritoneal dialysis (PD), iron status is often judged by transferrin saturation (TSAT) and ferritin. These can mislead when hypotransferrinaemia (low total iron-binding capacity, TIBC) coexists with low serum iron, artifactually elevating calculated TSAT.

Objectives :

We observed patients who appear iron-replete by conventional metrics yet exhibit features of functional iron restriction and a malnutrition–inflammation state.

Methodology :

We conducted a single-centre, retrospective observational study (2021–2025) using the Clinical Data Analysis and Reporting System (CDARS). Group A (Control): TIBC ≥ 44.8 μmol/L and TSAT 20–50%. Group B (Hypotransferrinaemic with Elevated TSAT): TSAT > 20% with TIBC < 44.8 μmol/L and serum iron < 10.7 μmol/L. Primary outcomes: ferritin, haemoglobin, albumin, C-reactive protein (CRP), and weekly erythropoiesis-stimulating agent (ESA; darbepoetin alfa) dose. Between-group comparisons used independent samples t-tests.

Result & Outcome :

Among 461 patients contributing 6,401 profile-level datapoints, Group B occurred in 310 patients (67%) and 1,252 profiles (24.2%); Group A accounted for 1,604 profiles (31.0%). Compared with controls, Group B had higher ferritin (mean 998.8 vs 519.0 µg/L, p < 0.001), lower haemoglobin (96.1 vs 108.5 g/L, p < 0.001), lower albumin (31.5 vs 37.2 g/L, p < 0.001), and higher CRP (8.0 vs 1.6 mg/L, p < 0.001). Variability was greater in Group B for ferritin (SD 2,033 vs 549 µg/L) and albumin (SD 5.54 vs 3.23 g/L), suggesting heterogeneous inflammatory burden. Group B required higher weekly ESA doses (41.9 vs 30.4 units, p = 0.025), consistent with anaemia resistance. The “hypotransferrinaemic pseudohyperTSataemic” phenotype is common in PD (present in 67% of patients) and associates with lower haemoglobin, hypoalbuminaemia, elevated CRP, and higher ferritin—indicative of malnutrition–inflammation and functional iron restriction. Reliance on higher ferritin and/or TSAT to infer adequate iron stores risks under-treating iron deficiency in this subgroup. Clinical decision making should explicitly integrate TIBC, serum iron, calculated TSAT, ferritin, albumin, and CRP to recognise this phenotype and avoid inappropriate withholding of iron therapy. Management should emphasise individualised assessment, nutritional optimisation, control of inflammation, judicious iron replacement, and evaluation of ESA responsiveness. Prospective cohorts and interventional trials are needed to clarify causality and test whether targeted nutritional, anti-inflammatory, and iron-repletion strategies improve haematologic control and patient outcomes.