Search Results (213)

Background/Objectives: Iron deficiency remains a prevalent condition, needing specific laboratory tests for diagnosis. This study aimed to evaluate whether routine complete blood cell count (CBC) parameters can be used within a machine learning framework to predict low ferritin and low transferrin saturation, used as biochemical markers of altered iron status, potentially supporting more targeted laboratory test utilization. Methods: In this single-center retrospective outpatient study, we analyzed 32,437 records from subjects undergoing both complete blood cell count and iron metabolism testing between 2023 and 2026. Low ferritin and low transferrin saturation were defined using sex-specific thresholds. Low ferritin was present in 14,344 subjects (44.2%), whereas low transferrin saturation was present in 7791 subjects (24.0%). After cleaning data and excluding incomplete records, demographic variables and CBC indices were tested as potential predictors. The dataset was split into training and test sets with stratified sampling. Multiple supervised machine learning models, including logistic regression, decision tree, random forest, XGBoost, support vector machine, k-nearest neighbors, and Naive Bayes, were trained. Hyperparameter tuning and model selection were performed using repeated stratified 10-fold cross-validation, optimizing the area under the curve (AUC). Model performance was assessed by AUC, sensitivity, and specificity, and validated on an independent test set. Results: All models showed predictive capability for low ferritin and low transferrin saturation using CBC parameters alone. Ensemble methods, especially random forest and XGBoost, reached the best performance (AUC values of 0.80–0.87 for ferritin and 0.85–0.96 for transferrin saturation). Sensitivity and specificity were balanced, supporting clinical screening applicability. Results were maintained across validation and confirmed in the test set. Prediction of transferrin saturation showed slightly higher accuracy than ferritin. Feature importance analysis identified mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red blood cell distribution width (RDW) as key predictors. Conclusions: CBC-based machine learning models may help identify subjects with low ferritin or low transferrin saturation, supporting subsequent targeted assessment of iron status. Full article

Background/Objectives: Anemia is frequently encountered in emergency departments (EDs). Although intravenous (IV) iron can be used as an alternative or adjunct to red blood cell (RBC) transfusion in selected hemodynamically stable patients, its use in the ED remains limited. This study described IV iron utilization and RBC transfusion patterns in ED patients with anemia and evaluated their associations with clinical outcomes. Methods: We conducted a single-center retrospective cohort study of patients who presented to a tertiary ED with hemoglobin (Hb) ≤ 10 g/dL between January 2019 and December 2021. Patients were categorized according to receipt of IV iron in the ED. Baseline characteristics, laboratory findings, transfusion practice, hospital length of stay (LOS), ICU admission, and in-hospital mortality were compared between groups. Results: Among 3340 patients, 89 (2.7%) received IV iron in the ED. IV iron recipients were older and had lower Hb levels than non-recipients. Gastrointestinal disorders were more frequent in the IV iron group (68.5% vs. 19.9%), and IV iron was commonly administered with ED RBC transfusion. ED transfusion (69.7% vs. 11.1%) and ICU admission (24.7% vs. 15.7%) were more frequent in the IV iron group. Among patients with available ferritin and transferrin saturation (TSAT), IV iron recipients had lower ferritin levels and more frequently showed ferritin-based or combined ferritin/TSAT findings suggestive of iron deficiency. In-hospital mortality was similar between groups (5.6% vs. 5.7%). Among hospitalized patients, median LOS was shorter in the IV iron group than in the non-IV iron group (6.6 vs. 9.7 days). Conclusions: IV iron was infrequently administered in ED patients with Hb ≤ 10 g/dL and was used mainly as an adjunct to RBC transfusion in older patients with gastrointestinal causes of anemia. Its association with shorter LOS should be interpreted cautiously. Structured ED-based anemia evaluation may help optimize IV iron use in selected patients. Full article

Obesity prevalence has increased globally, and metabolic bariatric surgery (MBS) is the most effective treatment for severe obesity. However, the impact of postoperative dietary counselling (DC) on clinical outcomes including weight is unclear. This review aims to assess the nature and impact of postoperative DC delivered by dietitians on clinical outcomes in adults undergoing post-MBS, focusing on weight change as the primary outcome, and body composition, nutritional status, biochemical parameters, and complications as secondary outcomes. Five databases (Medline, Embase, Web of Science, CINAHL, and Cochrane Library) were searched for observational studies and randomised controlled trials (RCTs) assessing DC related to weight change. Thirteen studies met the inclusion criteria (five RCTs and eight observational studies), involving 4173 individuals. Eight studies reported no significant difference in weight outcomes between the groups receiving DC and comparison groups. However, secondary outcomes such as nutritional status, complications, and levels of transferrin saturation, vitamin B12, and vitamin D showed improvements with more frequent DC. The components of DC delivered by dietitians varied, including advice on micronutrient supplements, protein intake, physical activity, transition diets, healthy eating, and mindful eating. Evidence supporting the efficacy of postoperative DC in promoting weight loss is limited by short-term assessment and inconsistencies in reporting weight outcomes, highlighting the need for long-term RCTs to ascertain its effectiveness. Full article

Background/Objectives: Autoimmune gastritis (AIG), celiac disease (CD), and gastric surgery (GS) often cause iron deficiency anemia (IDA) due to iron malabsorption. In this clinical context, IDA treatment is often challenging. The first-line IDA treatment is oral iron supplementation followed by intravenous (IV) iron administration when ineffective or not tolerated. Ferric carboxymaltose (FCM) showed efficacy in various clinical settings. Prospective data evaluating the efficacy of IV FCM in IDA patients secondary to iron malabsorption are scant. The aim of the current study was to assess the tolerability, efficacy, and QoL impact of IV FCM for the treatment of IDA patients with iron malabsorption. Methods: Study design: single-center, prospective observational study: n = 37 adults with AIG, CD, or GS with IDA receiving IV FCM were consecutively included. Endpoints were (i) safety tolerability, (ii) efficacy on IDA recovery (Hb normalization), and (iii) QoL impact. At baseline (T0) and 12 weeks after treatment (T12), a QoL-SF12 questionnaire was assessed. Complete blood count (CBC) and iron status (ferritin, iron, transferrin, transferrin saturation (TS)) were assessed at T0, 4 weeks (T4), and T12 after treatment. Results: Of the 37 IDA patients, 19 (51.4%) had AIG, 9 (24.3%) CD, and 9 (24.3%) GS; Based on Ganzoni’s formula, 24 (64.9%) patients received a single IV FCM infusion (mean ± SEM dosage of 975 ± 12 mg); 13 (35.1%) required two IV infusion sessions with a mean ± SEM cumulative dose of 1400 ± 77 mg. One patient (2.7%) experienced mild adverse events without need for treatment interruption or hospitalization. At T0, anemia was moderate in 7 (18.9%) patients and severe in 1 (2.7%). IDA recovery was achieved in 26 (70.3%) patients at T4 and in 29 (78.4%) at T12. At T4, mean ± SEM Hb increased from 10.8 ± 0.2 g/dL to 12.7 ± 0.1 g/dL, ferritin from 28.5 ± 11.2 ng/mL to 188.2 ± 25.7 ng/mL, and TS from 6.7 ± 0.5% to 23.7 ± 1.9% (p < 0.0001). At T12, mean ± SEM Hb further increased to 13.1 ± 0.2 g/dL (p < 0.05 vs. T4), ferritin slightly decreased to 125 ± 26.7 ng/mL, and TS to 22.7 ± 2.8%. At T12, nonsignificant increases in QoL scores relative to baseline were observed. Conclusions: IV FCM is a safe and effective treatment leading to IDA recovery in nearly 80% of patients at T12. Thus, when oral iron treatment is not feasible or has failed, IV FCM treatment might be considered a first-line therapeutic option for IDA consequent to iron malabsorption. Full article

Background/Objectives: Peripheral biomarkers for autism spectrum disorder (ASD) have shown mixed results in previous studies. In this study, complete blood count-derived immune-inflammatory markers, iron and micronutrient levels, and thyroid function were compared between drug-naïve preschoolers newly diagnosed with ASD and healthy controls. Additionally, the relationships between these markers, symptom severity, and developmental skills were examined. Methods: This retrospective case–control study included 62 children with ASD (aged 24–72 months) and 61 age-matched healthy controls. Symptom severity, behavioral traits, and developmental status were assessed using the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Denver II Developmental Screening Test (DDST), respectively. Composite inflammatory indices were calculated from hemogram data. Statistical analyses incorporated Holm–Bonferroni corrections for multiple comparisons and sex-stratified exploratory analyses of conditional associations using 95% bootstrap confidence intervals based on 5000 resamples. Results: Children with ASD demonstrated significantly lower mean corpuscular volume (MCV; d = 0.66, adj. p = 0.019), lower mean platelet volume (MPV; d = 0.58, adj. p = 0.034), and higher absolute lymphocyte counts (LYMPH; d = 1.10, adj. p = 0.019). Initial group differences in ferritin, serum iron, and transferrin saturation did not survive adjustment (adj. p > 0.05). Composite inflammatory indices were not significantly associated with clinical or developmental scores. Higher CARS and ABC scores correlated with lower personal–social and language scores on the DDST (p < 0.01). Furthermore, exploratory sex-stratified, conditional association analyses suggested preliminary basophil- and lymphocyte-related patterns in girls; however, these findings are strictly hypothesis-generating due to the small female sample size (n = 12). Conclusions: Newly diagnosed, drug-naïve preschoolers with ASD showed a distinct baseline blood profile, including lower MCV and MPV and higher lymphocyte counts. Clinical challenges were most evident in personal–social and language domains. While the primary diagnostic value of routine hemograms in this context appears limited, the exploratory sex-stratified basophil- and lymphocyte-related patterns require validation in adequately powered future cohorts. Full article

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global public health crisis, progressing to hepatic cirrhosis and hepatocellular carcinoma. This study investigated the causal role of systemic iron status in MASLD progression. Methods: A two-sample Mendelian randomization (MR) design was implemented, with genetic variants serving as instrumental variables for four core systemic iron biomarkers. Outcome data for hepatic steatosis (8785 cases; 912,105 controls) and hepatic fibrosis/cirrhosis (3798 cases; 904,599 controls) were extracted from the FinnGen and UK Biobank databases. Multiple complementary MR methodologies and three instrumental variable selection strategies were applied to ensure robust causal inference. Results: Genetically predicted higher serum iron (odds ratio, OR: 1.42, 95% confidence interval, 95% CI: 1.34, 1.50), ferritin (OR: 1.84, 95% CI: 1.55, 2.18), and transferrin saturation (TfSat, OR: 1.24, 95% CI: 1.19, 1.30), together with lower total iron-binding capacity (TIBC, OR: 0.81, 95% CI: 0.77, 0.85), were significantly associated with increased hepatic steatosis risk (p < 0.00625). Similar associations were observed for hepatic fibrosis/cirrhosis: serum iron (OR: 1.66, 95% CI: 1.29, 2.14), ferritin (OR: 2.52, 95% CI: 1.52, 4.18), TfSat (OR: 1.40, 95% CI: 1.19, 1.63), and reduced TIBC (OR: 0.70, 95% CI: 0.60, 0.81). MR-Bayesian model averaging prioritized serum iron (MIP: 0.85, ${\widehat{\theta }}_{\mathrm{MACE}}$: 0.295; PP: 0.725; ${\widehat{\theta }}_{\mathsf{\lambda }}$: 0.344) as the top-ranked factors for steatosis and TIBC (MIP: 0.604, ${\widehat{\theta }}_{\mathrm{MACE}}$: −0.240; PP: 0.476, ${\widehat{\theta }}_{\mathsf{\lambda }}$: −0.358) for fibrosis/cirrhosis. Conclusions: Elevated systemic iron status causally drives MASLD onset and progression, highlighting iron homeostasis and ferroptosis as potential targets for prevention and clinical management. Full article

Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis. This prospective single-center, non-randomized, single-arm cohort study enrolled renal transplant recipients with refractory anemia, defined as hemoglobin (Hb) ≤10 g/dL despite receiving the maximum doses of erythropoiesis-stimulating agents for 12 weeks. The studied parameters were Hb, ferritin, iron saturation index, glomerular filtration rate (eGFR), and C-reactive protein (CRP). Follow-up assessments were conducted at 4, 8, and 12 weeks after starting Roxadustat. The primary endpoint was the proportion of patients achieving Hb > 11 g/dL at 12 weeks. Secondary endpoints included changes from baseline in studied parameters and adverse effects. Twenty recipients (11 male, 9 female) with a median age of 69.0 years and a median time post-transplant of 62.5 months were included. Median baseline eGFR was 16.5 mL/min/1.73 m². At 12 weeks, 19 of 20 (95%) achieved Hb > 11 g/dL. Median Hb increased significantly from 9.1 g/dL to 11.5 g/dL, with a median individual change of +2.7 g/dL (IQR 1.7–3.4; p < 0.001). The only non-responder increased Hb from 9.5 to 10.2 g/dL. Ferritin decreased significantly over 12 weeks, whereas no statistically significant changes were observed in transferrin saturation, CRP, or eGFR. No serious adverse events were observed. In this prospective cohort, roxadustat was associated with short-term hemoglobin improvement and high Hb target attainment; however, these findings should be interpreted cautiously given the single-arm design and limited sample size. Full article

Background/Objectives: Blood iron biomarkers are commonly interpreted using fixed clinical reference intervals, although iron metabolism varies by age, sex, menopausal status, and race. This study aimed to characterize the distribution of iron biomarkers across demographic subgroups and to examine their distribution relative to commonly used reference intervals. Methods: In this cross-sectional study, 7990 adults (≥18 years) from the All of Us Research Program were classified as premenopausal women, postmenopausal women, men < 53 years, or men > 56 years. Serum iron, ferritin, total iron-binding capacity, unsaturated iron-binding capacity, and transferrin saturation (TSAT) were summarized across groups and compared descriptively with commonly used reference intervals. Results: Iron biomarkers varied across demographic groups. Mean serum iron was 82.3 µg/dL overall, with lower levels in premenopausal women (79.5 ± 36.7 µg/dL) and higher levels in men < 53 years (86.8 ± 41.8 µg/dL). Mean TSAT was 25.6% and generally located toward the lower end of commonly used reference ranges. Ferritin showed substantial variability, with higher mean levels in younger men (258.0 ± 581.0 ng/mL) and lower levels in premenopausal women (102.1 ± 224.9 ng/mL). Premenopausal women had higher iron-binding capacity, whereas older men had lower values. Black participants had lower serum iron and TSAT but higher ferritin compared with White participants. A substantial proportion of participants had values outside commonly used reference intervals, particularly for serum iron and TSAT. Conclusions: Iron biomarker distributions differ across demographic subgroups and may not be fully reflected by commonly used reference intervals. These findings highlight the importance of context-specific interpretation and underscore the need for further studies to evaluate the applicability of current reference intervals across diverse populations. Full article

Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure. Full article

We evaluated the interplay between systemic total antioxidant capacity (TAC), oxidative stress (OS) (lipid hydroperoxides), inflammation, iron status, and oral contraception (OC) use in 182 healthy 23-year-old women (76 OC-users, and 106 non-OC-users). In all women, blood TAC (FORD units) values were significantly inversely associated with OS (FORT units), high-sensitivity C-reactive protein (hsCRP), and transferrin; and positively associated with transferrin saturation (TfS%). No significant associations were observed for hemoglobin, hematocrit, red blood cells, serum iron, soluble transferrin receptor (sTfR), sTfR/log(ferritin) ratio (sTfR-F index), ferritin, folate, uric acid, or creatinine. OS hydroperoxides were positively associated with hsCRP and transferrin, and inversely associated with TfS%. sTfR was positively correlated with hydroperoxides in non-OC-users and with folate in all women and non-OC-users, but was not associated with hsCRP in any group. The combined abnormal condition of low TAC and elevated OS (n = 71) was significantly more frequent among OC-users (OR = 39.0), women with hsCRP ≥ 3 mg L⁻¹ (OR = 10.1), transferrin ≥ 330 mg dL⁻¹ (OR = 6.58), and smokers (OR = 3.76). OC use modulated the TAC/OS balance and inflammation. Low TAC and elevated OS may impact health status. Enhanced TAC/OS knowledge may increase awareness of effects of OC use among fertile-age women. Ferritin was independent of TAC/OS status and OC use, supporting its reliability as an iron biomarker. Full article

Background/Objectives: Higher iron doses are used in the anemia treatment of hemodialysis patients, which allows for lower doses of erythropoiesis-stimulating agents; however, there are concerns regarding the risk of iron toxicity. This study aimed to evaluate the potential toxicity of iron deposition in prevalent hemodialysis patients on iron therapy and its relationship with parameters used to assess iron status, plasma protein oxidation, and cellular iron toxicity. Methods: Magnetic resonance imaging was performed in 56 patients to assess hepatic iron deposition, which was related to clinical and analytical parameters. In patients included in the first and fourth quartiles, according to hepatic iron deposition, plasma protein oxidative stress was quantified, as were iron and cytokine levels in peripheral blood mononuclear cells (PBMCs). Results: Patients with higher hepatic iron deposition had a longer time on hemodialysis (42.0 ± 43.0 vs. 4.9 ± 3.4 months, p < 0.001) and higher ferritin levels (1200 ± 516 vs. 429 ± 278 ng/mL, p < 0.001) than those with lower hepatic iron deposition, without differences in transferrin saturation or hepatic enzyme serum concentration. No differences were found in plasma protein oxidation, iron content, or cytokine mRNA content in PBMCs, except for a decrease in IL-6 levels in patients with higher hepatic iron deposition. Conclusions: Patients with longer hemodialysis times had higher iron stores, suggesting that iron treatment over time increases hepatic iron deposition. No parameters supporting increased toxicity in patients with higher hepatic iron deposition were observed. Full article

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article

Individuals with C282Y/C282Y in the hemochromatosis HFE gene have increased iron levels, which catalyze the formation of reactive oxygen species, and an increased risk of diabetes. These individuals may have disproportionately lower hemoglobin A1c (HbA1c) due to increased erythrocyte turnover, decreased erythrocyte counts, and/or an increased mean corpuscular hemoglobin concentration (MCHC). In the Copenhagen General Population Study (N = 103,734) and the Danish General Suburban Population Study (GESUS, N = 20,003), we investigated the association between C282Y/C282Y (N = 399) and other HFE genotypes with erythrocyte count, MCHC, mean corpuscular volume (MCV), red cell distribution width (RDW), and high-sensitivity C-reactive protein (hsCRP). In GESUS, we additionally investigated the association with oxidative stress (by 8-oxo-7,8-dihydroguanosine and 8-oxo-7,8-dihydro-2′-deoxyguanosine), reticulocyte count, reticulocyte hemoglobin, reticulocyte percentage as a proxy for erythrocyte turnover, and HbA1c in linear regressions adjusted for age, sex, cohort, and blood donation. We investigated the mediation between HFE genotype and HbA1c. Compared to non-carriers, individuals with C282Y/C282Y had increased p-iron, transferrin saturation, ferritin, hsCRP, oxidative stress, reticulocyte counts, reticulocyte percentage (1.24% vs. 1.06%, p = 1.7 × 10⁻⁵) as a proxy for erythrocyte turnover, MCHC (344 vs. 340 g/L, p = 1.7 × 10⁻¹²), MCH, MCV, reticulocyte hemoglobin, p-glucose (5.6 vs. 5.4, p = 0.007), bilirubin, and LDH and decreased RDW, erythrocyte counts (4.49 × 10¹²/L vs. 4.61 × 10¹²/L, p = 6.1 × 10⁻¹¹), estimated erythrocyte survival, and HbA1c (36 vs. 38 mmol/mol, p = 0.01). The associations were similar, although attenuated, for other HFE genotypes. The association between the HFE genotype and decreased HbA1c was partially mediated by increased transferrin saturation, MCHC, MCV, and decreased erythrocyte count, but not by hsCRP, reticulocyte count, oxidative stress, or blood donation. In conclusion, while C282Y/C282Y and other HFE genotypes increased erythrocyte turnover, the disproportionately decreased HbA1c level was explained by fewer but larger erythrocytes filled with more hemoglobin and removed earlier from circulation, thus diluting the relative concentration of intracellular glucose per hemoglobin molecule. Full article

Background: The population of elderly patients undergoing chronic hemodialysis is increasing, and anemia represents a frequent complication. The aim of our study was to evaluate the association between ultrafiltration rate (UFR) in hemodialysis and erythropoietin (EPO) response in elderly patients with end-stage kidney disease (ESKD). Methods: This was a multicenter, retrospective observational study, involving elderly patients (aged 65 years or more) under chronic hemodialysis therapy. Individuals were divided into two groups according to the UFR adjusted to weight (UFR/W): lower (UFR-N) or higher (UFR-H) than 10 mL/h/kg. EPO resistance index (ERI) was calculated. We evaluated the hemogram, reticulocyte count, and quantified markers of iron metabolism and inflammation. Results: A total of 193 patients were enrolled in the study: 141 patients met criteria for inclusion in UFR-N group and 52 in UFR-H group. Compared to UFR-N, patients in the UFR-H group presented significantly higher doses of erythropoiesis-stimulating agents (ESA) and ERI values, with similar hemoglobin (Hb) and inflammatory markers levels. In a sub-analysis, within patients presenting transferrin saturation (TSAT) lower than 20%, a more marked difference in ERI between UFR groups was observed, being much higher in UFR-H compared with UFR-N. In this subgroup (UFR-H with lower TSAT), levels of hepcidin were lower than in the other subgroups. Conclusions: Our data show that UFR appears to be a contributing factor of ESA response in elderly patients under hemodialysis, particularly in those with lower iron availability. These findings suggest that inadequate weight control and/or UF prescription seem to aggravate ESA needs to achieve target Hb. Full article

Background: Iron deficiency (ID) is common among people with chronic kidney disease (CKD) and/or heart failure (HF). Despite the additional burden ID causes among people with CKD and HF, there is considerable uncertainty surrounding the best way to diagnose it and, subsequently, identify who is most likely to benefit from receiving iron therapy. Methods: This manuscript reports the markers and thresholds used in ID diagnosis, treatment, and management in the UK by nephrologists and cardiologists who manage people with chronic kidney disease or heart failure, as well as investigating future challenges and questions that remain unanswered. The research involved three stages: an online questionnaire, individual interviews, and a panel meeting, which discussed the findings from the first two stages. Results: The panel concluded that there is no robust definition of iron deficiency that can be applied to chronic kidney disease and heart failure. Existing methods of diagnosing iron deficiency come with various problems; a transferrin saturation of <20% is the most popular, but it is not regarded as a perfect solution. Transferrin saturation is also the most popular way of assessing the success of iron deficiency treatment. Clinicians generally do not vary treatment regimens based on severity or subgroups. There are large variations in monitoring and the ability to administer iron therapy in secondary care. Conclusions: There is a clear need to consolidate current approaches to diagnosing and treating iron deficiency in people with chronic kidney disease and/or heart failure. Simple markers and thresholds, and simple strategies to implement them are required. Full article