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Concept: Transferrin saturation


The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC). Male Wistar rats were submitted to 5/6 nephrectomy (Nx) to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine) was administrated (1.5 mM/KgBW, intravenously) 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1–Nx (n = 7); 2–Nx+NAC (n = 6); 3–Nx+Gd (n = 7); 4–Nx+NAC+Gd (4.8 g/L in drinking water), initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6). This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW), proteinuria (mg/24 hs), serum iron (µg/dL); serum ferritin (ng/mL); transferrin saturation (%), TIBC (µg/dL) and TBARS (nmles/ml). Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

Concepts: Renal failure, Kidney, Nephrology, Dialysis, Renal function, Transferrin, Transferrin saturation, Serum iron


There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model.

Concepts: Gene, Helicobacter pylori, Transferrin, Human iron metabolism, Transferrin saturation, Serum iron, Iron metabolism, Total iron-binding capacity


AIMS: Acute Helicobacter pylori infection is associated with transient hypochlorhydria. In H pylori-associated atrophy, hypochlorhydria has a role in iron deficiency (ID) through changes in the physiology of iron-complex absorption. The aims were to evaluate the association between H pylori-associated hypochlorhydria and ID in children. METHODS: Symptomatic children (n=123) were prospectively enrolled. Blood, gastric juice and gastric biopsies were taken, respectively, for haematological analyses, pH assessment and H pylori determination, and duodenal biopsies for exclusion of coeliac disease. Stool samples were collected for parasitology/microbiology. Thirteen children were excluded following parasitology and duodenal histopathology, and five due to impaired blood analysis. RESULTS: Ten children were hypochlorhydric (pH>4) and 33 were H pylori positive. In H pylori-positive children with pH>4 (n=6) serum iron and transferrin saturation levels % were significantly lower (p<0.01) than H pylori-positive children with pH≤4. No differences in ferritin, or total iron binding capacity, were observed. In H pylori-negative children with pH>4, iron and transferrin saturation were not significantly different from children with pH≤4. CONCLUSIONS: Low serum iron and transferrin in childhood H pylori infection is associated with hypochlorhydria. In uninfected children, hypochlorhydria was not associated with altered serum iron parameters, indicating a combination of H pylori infection and/or inflammation, and hypochlorhydria has a role in the aetiology of ID. Although H pylori-associated hypochlorhydria is transient during acute gastritis, this alters iron homeostasis with clinical impact in developing countries with a high H pylori prevalence.

Concepts: Gastroenterology, Stomach, Helicobacter pylori, Iron deficiency anemia, Gastritis, Transferrin, Transferrin saturation, Total iron-binding capacity


OBJECTIVES: To evaluate in a large, nationally representative cohort the association between high serum transferrin saturation (TS) and hospital length of stay and mortality in older adults. DESIGN: Prospective cohort. SETTING: Longitudinal analyses of the Third National Health and Nutrition Examination Survey linked to Medicare claims from 1991 through 2006. PARTICIPANTS: Medicare beneficiaries aged 65 and older at baseline. MEASUREMENTS: Transferrin saturation collected on each participant at baseline was characterized as <20.0%, 20.0% to 54.9%, and 55.0% and greater. Length of stay in the hospital and death in the hospital were primary outcomes. Analyses were adjusted for age, sex, race and ethnicity, education, and severity of illness. RESULTS: Individuals hospitalized during the study period (79.4%) with high (odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.05-6.12) or low (OR = 1.31, 95% CI = 1.07-1.62) TS had a significantly greater risk of death than those with moderate TS. Individuals with high TS had longer average length of stay per hospitalization (11.1 days, (standard error, SE 1.7 days), P = .01) than those with moderate TS (8.4 (0.3) days). Individuals with high TS also had more hospital days per year (8.6 (2.0) days, P = .04) than those with moderate TS (6.7 (0.5) days). CONCLUSION: High TS is associated with longer length of stay and death in the hospital (unweighted N = 3,847, weighted N = 28,395,464).

Concepts: Epidemiology, Death, Hospital, Gerontology, Ageing, Normal distribution, Transferrin, Transferrin saturation


Two reference measurement procedures are presented here that allow the determination of the iron saturation in human transferrin, based on different molecular properties. The results, directly derived from the number of ions bound to the protein molecule, are traceable to the SI. Up to now, the iron saturation has only been deduced indirectly from the amount-of-substance ratio of serum iron to transferrin in serum. Interlaboratory tests have shown the need for more accurate methods, as the results from many participant test samples for both parameters do not lie within the acceptable range of deviation given by relevant guidelines when different methods or kits are applied. Using isotope dilution, an HPLC ICP-MS procedure was developed in compliance with the requirements of a primary reference measurement procedure. In this manner, the iron saturation was measured with an associated relative expanded measurement uncertainty of 4%. Based on the results, a straightforward Raman procedure was evolved, which allows the determination of the iron saturation in transferrin with an associated relative expanded uncertainty of 7%.

Concepts: Oxygen, Measurement, Metrology, Test method, Uncertainty, Transferrin, Transferrin saturation, Total iron-binding capacity


Background. Unbound iron binding capacity (UIBC) in serum, which is s-total iron binding capacity (2 times s- transferrin) minus s-iron, may be a more accurate marker of empty iron stores than serum transferrin saturation. Previously we have shown this for healthy females of childbearing age. Methods. Now we used receiver operating characteristic (ROC) curve analysis to compare the diagnostic accuracy of s-iron, s-transferrin, s-transferrin saturation and s-UIBC in diagnosing empty iron stores in 29,251 female and 19,652 male outpatients. Empty iron stores were defined as s-ferritin less than 10, 15 or 20 μg/L. Results. At all definitions of empty iron stores s-UIBC had a better diagnostic accuracy than the other tests in both male and female outpatients, with an area under the ROC curve of 0.85-0.97. Also in subpopulations with elevated s-CRP or low b-hemoglobin s-UIBC was more accurate than the other tests. All tests performed better in males than in females, and generally they were more accurate in adults than in children. Conclusion. When diagnosing empty iron stores calculation of s-UIBC is a better way to utilize the information in s-iron and s-transferrin than the calculation of s-transferrin saturation.

Concepts: Male, Female, Receiver operating characteristic, Transferrin, Transferrin saturation, Serum iron, Total iron-binding capacity


AIMS AND OBJECTIVES: To determine whether the use of a nurse-driven protocol in the haemodialysis setting is as safe and effective as traditional physician-driven approaches to anaemia management. BACKGROUND: The role of haemodialysis nurses in renal anaemia management has evolved through the implementation of nurse-driven protocols, addressing the trend of exceeding haemoglobin targets and rising costs of erythropoietin-stimulating agents. DESIGN: Retrospective, non-equivalent case control group design. METHODS: The sample was from three haemodialysis units in a control group (n = 64) and three haemodialysis units in a protocol group (n = 43). The protocol group used a nurse-driven renal anaemia management protocol, while the control group used a traditional physician-driven approach to renal anaemia management. All retrospective data were obtained from a provincial renal database. Data were analysed using chi-square tests and t-tests. Patient outcomes examined were haemoglobin levels, transferrin saturation levels, erythropoietin-stimulating agents use and intravenous iron use. Cost comparisons were determined using average use of erythropoietin-stimulating agents and intravenous iron. RESULTS: Control and protocol groups reached haemoglobin target levels. In the protocol group, 75% reached transferrin saturation target levels in comparison with 25% of the control group. Use and costs for iron was higher in the control group, while use and costs for erythropoietin was higher in the protocol group. The higher usage of erythropoietin-stimulating agents was potentially related to comorbid conditions amongst the protocol group. CONCLUSIONS: A nurse-driven protocol approach to renal anaemia management was as effective as the physician-driven approach in reaching haemoglobin and transferrin saturation levels. Further examination of the use and dosing of erythropoietin-stimulating agents and intravenous iron, their impact on haemoglobin levels related to patient comorbidities and subsequent cost effectiveness of protocols is required. RELEVANCE TO CLINICAL PRACTICE: Using a nurse-driven protocol in practice supports the independent nursing role while contributing to safe patient outcomes.

Concepts: Hemoglobin, Erythropoietin, Iron, Costs, Anemia, Iron deficiency anemia, Comorbidity, Transferrin saturation


Iron and the iron regulatory hormone hepcidin, major determinant of body iron distribution, are hypothesized to play a role in cardiovascular disease. Here, we assess the associations of hepcidin as well as ferritin, iron, total iron-binding capacity, and transferrin saturation (ie, iron parameters) with noninvasive measurements of atherosclerosis in men and women of a population-based cohort.

Concepts: Blood vessel, Cardiovascular disease, Gender role, Transferrin, Transferrin saturation, Serum iron, Iron metabolism, Total iron-binding capacity


Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data.

Concepts: Genetics, Genotype, Cirrhosis, Zygosity, Liver disease, Ferritin, Transferrin saturation, Iron metabolism


Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigate associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D.

Concepts: Diabetes mellitus type 2, Diabetes mellitus, Anemia, The Association, Iron deficiency anemia, Transferrin saturation, Iron deficiency, Iron metabolism