Cytomorphometric analysis of buccal mucosal cells in iron deficiency anemia: A cross-sectional study.

Background: Worldwide, at any given moment, more individuals have iron deficiency anemia (IDA) than any other health problems. Very few studies have been conducted to evaluate changes in oral mucosa in IDA. The present study is undertaken for cytomorphometric analysis of buccal mucosal cells in IDA. Nuclear diameter (ND), cell diameter (CD), nuclear area (NA), cell area (CA), and nuclear-cytoplasmic ratio (N/C) are measured and compared in buccal mucosal cells of IDA patients and controls. Aims: To evaluate cytomorphometric changes in epithelial cells of oral mucosa in IDA and to compare these changes with the controls. Settings and Design: A cross-sectional study. Methods and Materials: Forty cases of IDA and forty cases of control group were selected for the study. IDA cases were diagnosed with decreased Hb level, MCV, MCH, MCHC and confirmed by decreased serum iron and increased total iron-binding capacity levels. Cytomorphometric analysis of buccal mucosa was performed to study CA, CD, NA, ND, and N/C ratio. Statistical Analysis Used: Statistical analysis was done using t- test in SPSS software version 4. Result: Results of our study showed increased cell area, cell diameter, nuclear area, nuclear diameter, and nuclear-cytoplasmic ratio in anemic group as compared to controls. Conclusion: The study suggests that individuals with IDA regardless of clinically visible oral lesions show cytological changes in oral mucosal epithelium. Knowledge of quantitative alterations in oral epithelial cells of IDA patients is important as these alterations are similar to those seen in precancerous and radiation-induced changes. Cytomorphometry is an efficient tool to understand the extent of cellular changes that occur in oral epithelial cells in IDA.

Risk factors and clinical features associated with basal ganglia manganese deposition in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: T1-hyperintensity of the basal ganglia (BG) due to manganese deposition is a known radiologic finding in patients with hereditary hemorrhagic telangiectasia (HHT), but risk factors and associated clinical manifestations are unclear. This study conducted a quantitative analysis of the association of T1-hyperintensity in HHT patients with specific risk factors, signs, and symptoms. METHODS: Patients seen at our center between 2005 and 2020 with a definitive diagnosis of HHT who had an available non-contrast T1-weighted brain MRI were included. Hyperintensity was evaluated using oval regions of interest measurements. The BG: thalamus intensity ratio was used to quantitatively evaluate T1-hyperintensity. Patient laboratory values and clinical findings were collected from electronic medical records. Hyperintensity was analyzed for its association with laboratory values, and clinical findings. Variables were analyzed through regression analysis. RESULTS: A total of 239 patients were included in this study. On 1.5 T scanners, values that were significant on multivariable regression analysis were age (p < .001), hepatic AVMs (p < .001), iron deficiency anemia (p = .0021), and cirrhosis (p = .016). On 3 T scanners, values that were significant on multivariable analysis were hepatic AVMs (p = .0024) and cirrhosis (p = .0056). On 3 T scanners, hyperintensity was significantly associated with tremor (OR = 1.17, p = .033), restless leg syndrome (OR = 1.22, p = .0086), and memory problems (OR = 1.17, p = .046). CONCLUSIONS: BG hyperintensity due to manganese deposition is significantly associated with hepatic risk factors on 1.5 T and 3 T scanners and iron deficiency anemia on 1.5 T scanners. On 3 T scanners, T1-hyperintensity is associated with neuropsychiatric signs and symptoms, such as tremor, restless leg syndrome, and memory problems.

Influence of Helicobacter Pylori Infection on Hepcidin Expression in the Gastric Mucosa.

BACKGROUND: Hepcidin is an antimicrobial peptide and a key hormone involved in iron homeostasis. Hepcidin level is elevated in the serum during the course of Helicobacter pylori infection and hepcidin is considered to contribute to iron deficiency anemia. However, it is unclear whether H. pylori infection influences hepcidin expression in the gastric mucosa. METHOD: In this study, 15 patients with H. pylori-infected nodular gastritis, 43 patients with H. pylori-infected chronic gastritis, and 33 patients without H. pylori infection were enrolled. Endoscopic biopsy, and histological and immunohistochemical analysis were performed to evaluate the expression of hepcidin and its distribution in the gastric mucosa. RESULT: Hepcidin was strongly expressed in the lymph follicles of patients with nodular gastritis. The detection rates of gastric hepcidin-positive lymphocytes in patients with nodular gastritis and chronic gastritis were significantly higher than that without H. pylori infection. Moreover, regardless of the H. pylori infection status, hepcidin was expressed in the cytoplasm and intracellular canaliculi of gastric parietal cells. CONCLUSION: Hepcidin is expressed at a steady state in gastric parietal cells, and H. pylori infection may induce hepcidin expression in lymphocytes present in the gastric mucosal lymphoid follicles. This phenomenon may be associated with systemic hepcidin overexpression and iron deficiency anemia in patients with H. pylori-infected nodular gastritis.

Paleoepidemiology of cribra orbitalia: Insights from early seventh millennium BP Con Co Ngua, Vietnam.

OBJECTIVES: We test the hypothesis that the condition(s) leading to the development of cribra orbitalia at Con Co Ngua, an early seventh millennium sedentary foraging community in Vietnam, effectively reduced the resilience of the population to subsequent health/disease impacts. An assessment of both the implications and potential etiology of cribra orbitalia in this specific population is carried out. METHODS: The effective sample included 141 adults aged ≥15 years (53 females, 71 males, and 17 unknown sex) and 15 pre-adults aged ≤14 years. Cribra orbitalia was identified by way of cortical bone porosity of the orbital roof initiated within the diplöic space, rather than initiated subperiosteally. The approach is also robust to the misidentification of various pseudo-lesions. Resultant data was analyzed using Kaplan-Meier survival analysis. RESULTS: Median survival is higher in adults aged ≥15 years without cribra orbitalia than those with this lesion. For the pre-adult cohort, the opposite pattern is seen where median survival is higher in those with cribra orbitalia than those without. CONCLUSION: Adults displayed increased frailty and pre-adults increased resilience with respect to cribra orbitalia. The differential diagnosis for a survival analysis of adults and pre-adults with and without cribra orbitalia included iron deficiency anemia and B12/folate deficiency, parasitism (including hydatid disease and malaria) in addition to thalassemia. The most parsimonious explanation for observed results is for both thalassemia and malaria being the chief etiological agents, while appreciating these conditions interact with, and can cause, other forms such as hematinic deficiency anemias.

Effects of chronic Helicobacter pylori strain PMSS1 infection on whole brain and gastric iron homeostasis in male INS-GAS mice.

Iron deficiency, the most common micronutrient deficiency in humans, is associated with long-term deficits in cognition and memory if left untreated. Infection with the gastric pathogen Helicobacter pylori has been linked to iron deficiency anemia (IDA). The H. pylori virulence factor cytotoxin-associated gene A (cagA) is proposed to be especially pertinent in iron deficiency. Male INS-GAS/FVB mice were infected with the CagA+ strain pre-murine Sydney strain 1 (PMSS1) for 12-13 or 27-29 weeks to investigate the role of chronic H. pylori infection in iron deficiency and neurological sequelae. Mice at both timepoints demonstrated significantly elevated gastric histopathology scores and inflammatory cytokines compared to sham-dosed controls. However, only mice at 27-29 weeks post infection had changes in hematological parameters, with significantly decreased erythrocyte count, hematocrit, serum hemoglobin, and increased serum total iron binding capacity. Gastric transcription of iron-regulatory genes Hamp and Bmp4 were significantly downregulated at both timepoints. In the brain, iron-dependent myelingergic and synaptic markers were significantly downregulated at 27-29 weeks. These results indicated that long-term infection of the CagA + PMSS1 strain of H. pylori in this study caused anemia, altered gastric iron homeostasis, and neurological changes similar to those reported in other rodent H. pylori CagA- strain infection models.

[Research progress on the regulation mechanisms of iron metabolism in anemia of chronic disease].

Anemia of chronic disease (ACD), complicated by various chronic inflammatory diseases, is the second most prevalent type of anemia after iron deficiency anemia in the world. ACD significantly reduces the life quality of patients with chronic diseases, and represents an independent poor prognostic factor in certain chronic diseases. A large body of studies has demonstrated that most of anemia is related to abnormal iron metabolism. In the past decade, hepcidin, as a key factor in regulating iron metabolism, has attracted enormous attention due to its important role in the pathogenesis of ACD. This article reviews the research progress on the role and underlying regulatory mechanisms of hepcidin in ACD. We also discuss the potential of hepcidin as an effective therapeutic target for ACD treatment, in order to provide a new maneuver for improving the quality of ACD patients' life.

[Clinical management of autoimmune gastritis]. / Autoimmungastritis.

Autoimmune gastritis (AIG) is a chronic immune-mediated inflammation of the gastric corpus/fundus mucosa leading to progressive atrophy of the oxyntic gastric glands (AOM) and their consecutive loss of function. Possible clinical consequences of AIG include iron deficiency anemia, pernicious anemia, gastric neuroendocrine tumors (gNET), and gastric adenocarcinoma. This article provides a review of interdisciplinary aspects of the diagnosis and treatment of AIG.

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Interrelations between Iron and Vitamin A-Studied Using Systems Approach.

A deficiency of vitamin A (VAD) and iron is the most common nutritional problem affecting people worldwide. Given the scale of the problem, the interactions between vitamin A and iron levels are widely studied. However, the exact mechanism of the impact of vitamin A on the regulation of iron metabolism remains unclear. An extremely significant issue becomes a better understanding of the nature of the studied biological phenomenon, which is possible by using a systems approach through developing and analyzing a mathematical model based on a Petri net. To study the considered system, the t-cluster analysis, the significance analysis, and the analysis of the average number of transition firings were performed. The used analyses have allowed distinguishing the most important mechanisms (both subprocesses and elementary processes) positively and negatively regulating an expression of hepcidin and allowed to distinguish elementary processes with a higher frequency of occurrence compared to others. The analysis also allowed to resolve doubts about the discrepancy in literature reports, where VAD leads to positive regulation of hepcidin expression or to negative regulation of hepcidin expression. The more detailed analyses have shown that VAD more frequently positively stimulates hepcidin expression and this mechanism is more significant than the mechanism inhibiting hepcidin expression indirectly by VAD.

Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: "Can the Promise Be Kept?"

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

Relationship between duodenal microbiota composition, clinical features at diagnosis, and persistent symptoms in adult Coeliac disease.

BACKGROUND: Duodenal dysbiosis has been suggested to possibly influence the clinical manifestations of coeliac disease (CD), both at onset and when symptoms persist despite a gluten-free diet (GFD). AIMS: To evaluate the relationship between duodenal microbiota composition and: i) clinical phenotype of untreated CD (UCD); ii) presence and type of persistent symptoms despite a satisfactory serological and histological response to a strict GFD. METHODS: Duodenal microbiota was analyzed by 16S rRNA sequencing and compared with i) clinical features in 12 adult UCD patients; ii) presence/absence and type of persistent symptoms (diarrhea-predominant vs. non-diarrhea predominant) in 25 adult treated coeliac patients (TCD) on a strict GFD. RESULTS: UCD with iron deficiency anemia (IDA) had a pro-inflammatory shift in their duodenal microbiota (reduction of Firmicutes, p = 0.03; increase of beta-Proteobacteria, p = 0.02) than those without IDA. TCD with persistent diarrhea showed a reduction of Actinobacteria (p = 0.03) and Rothia spp (p = 0.046) compared to TCD suffering from other type of persistent symptoms. CONCLUSION: A distinctive duodenal microbiota profile is associated with IDA in UCD, and diarrhea-predominant persistent symptoms in TCD. Clinical interventions may include reconsidering patients presenting with IDA as a specific disease subtype, and dietary rebalancing if diarrhea persists despite histological response to a GFD.

Prediction of anemia at delivery.

We aimed to assess risk factors for anemia at delivery by conducting a secondary analysis of a prospective cohort study database including 1527 women who delivered vaginally ≥ 36 gestational weeks. Anemia (Hemoglobin (Hb) < 10.5 g/dL) was assessed at delivery. A complete blood count results during pregnancy as well as maternal and obstetrical characteristics were collected. The primary endpoint was to determine the Hb cutoff between 24 and 30 gestational weeks that is predictive of anemia at delivery by using the area under the curve (AUC) of the receiver operating characteristic curve. Independent risk factors for anemia at delivery were assessed using stepwise multivariable logistic regression. Hb and infrequent iron supplement treatment were independent risk factors for anemia at delivery (OR 0.3 95%CI [0.2-0.4] and OR 2.4 95%CI [1.2-4.8], respectively; C statistics 83%). Hb 10.6 g/dL was an accurate cutoff to predict anemia at delivery (AUC 80% 95%CI 75-84%; sensitivity 75% and specificity 74%). Iron supplement was beneficial to prevent anemia regardless of Hb value. Altogether, Hb should be routinely tested between 24 and 30 gestational weeks to screen for anemia. A flow chart for anemia screening and treatment during pregnancy is proposed in the manuscript.Trial registration: ClinicalTrials.gov Identifier: NCT02434653.

Association of Myeloperoxidase Gene Polymorphism With Iron Deficiency Anemia in Turkish Children.

This study was performed to investigate the gene polymorphisms of the myeloperoxidase (MPO) enzyme and to determine whether MPO gene polymorphisms influence the response to iron therapy in pediatric patients with iron deficiency anemia (IDA). In this case-control study, 50 Turkish children with IDA and 50 healthy controls were enrolled. Three MPO gene alleles were selected for genotyping in the study: GG, AG, and AA. The relationships of alleles with IDA were analyzed and compared in patients and controls. Pretreatment and posttreatment laboratory parameters and gene polymorphisms were compared in the patient group. There was a significant difference between patients with IDA and controls regarding genotype frequencies of the AA, GG, and AG alleles (P=0.005). However, the AG allele was found to be associated with variations in hemoglobin, red blood cell, hematocrit, mean corpuscular volumes, and mean corpuscular Hb concentrations levels. The frequency of AA, GG, and AG alleles of the MPO gene was potentially associated with changes in iron metabolism and the AG allele led to variations in various hemogram parameters.

The misogyny of iron deficiency.

Anaemia is common, particularly in women and the commonest underlying cause, iron deficiency, is often overlooked. Anaemia is associated with increased morbidity and mortality in patients undergoing anaesthesia; however, women are defined as being anaemic at a lower haemoglobin level than men. In this narrative review, we present the history of iron deficiency anaemia and how women's health has often been overlooked. Iron deficiency was first described as 'chlorosis' and a cause of 'hysteria' in women and initial treatment was by iron filings in cold wine. We present data of population screening demonstrating how common iron deficiency is, affecting 12-18% of apparently 'fit and healthy' women, with the most common cause being heavy menstrual bleeding; both conditions being often unrecognised. We describe a range of symptoms reported by women, that vary from fatigue to brain fog, hair loss and eating ice. We also describe experiments exploring the physical impact of iron deficiency, showing that reduced exercise performance is related to iron deficiency independent of haemoglobin concentration, as well as the impact of iron supplementation in women improving oxygen consumption and fitness. Overall, we demonstrate the need to single out women and investigate iron deficiency rather than accept the dogma of normality and differential treatment; this is to say, the need to change the current standard of care for women undergoing anaesthesia.

The effect of iron deficiency and anaemia on women's health.

Iron deficiency and anaemia are global health problems and major causes of morbidity in women. Current definitions of anaemia in women are historic and have been challenged by recent data from observational studies. Menstrual loss, abnormal uterine bleeding and pregnancy put women at risk of developing iron deficiency which can result in severe fatigue, reduced exercise capacity and poor work performance. Iron deficiency and anaemia during pregnancy are associated with adverse maternal and fetal outcomes, including neurocognitive deficits in children born to iron-deficient mothers. Both iron deficiency and anaemia are common in women undergoing surgery but their association with poor outcomes remains uncertain. The enduring burden of iron deficiency and anaemia in women suggests that current strategies for recognition, prevention and treatment are limited in their utility. Improvements in our understanding of iron homeostasis and the development of new iron preparations, which are better absorbed with fewer side-effects, may improve therapeutic effectiveness of oral iron. Intravenous iron is efficacious for correcting anaemia rapidly but high-quality data on patient-centred outcomes and cost-effectiveness are currently lacking. Many recommendations for the treatment of iron deficiency and anaemia in national guidelines are not supported by high-quality evidence. There is a need for robust epidemiological data and well-designed clinical trials. The latter will require collaborative working between researchers and patients to design studies in ways that incorporate patients' perspectives on the research process and target outcomes that matter to them.

Evaluation of angiogenic signaling molecules associated with reactive thrombocytosis in an iron-deficient rat model.

BACKGROUND: Iron deficiency anemia (IDA)-induced reactive thrombocytosis can occur in children and adults. The underlying mechanism for this phenomenon is indeterminate. Traditional cytokines such as thrombopoietin (TPO), interleukin-6 (IL-6), and IL-11 involved in megakaryopoiesis have not been shown to be the cause. Recent studies suggest that growth factors and signaling molecules involved with angiogenesis influence the proliferation and differentiation of megakaryocytes. METHODS: We investigated the possible association between angiogenic cytokines with reactive thrombocytosis due to IDA in an iron-deficient (ID) rat model. Complete blood count, iron panels, and TPO levels were measured at baseline and 5 weeks later in both control (C) and ID rats. Angiogenic cytokines were evaluated in the bone marrow in all rats. RESULTS: We successfully induced IDA in our rats by phlebotomy and reduced iron diet. We did not find an increase of TPO in ID rats. A review of the bone marrow showed an increase in the number of megakaryocytes, vascular structures, as well as increased intensity of stain for vascular endothelial growth factor (VEGF), and CXC chemokine receptor 4 (CXCR4) in rats with IDA compared to controls. CONCLUSIONS: Our results of histological bone marrow data suggest an important role for angiogenesis in the development of IDA-induced thrombocytosis. IMPACT: Thrombocytosis is common with IDA in both children and adults, but the mechanism is unclear. We confirmed that TPO is not the major driver of iron deficiency-associated thrombocytosis. We confirmed the increase in the number of megakaryocytes in the bone marrow despite stable TPO levels. We provided evidence supporting an important role of angiogenesis in megakaryocytopoiesis/thrombopoiesis with increased vascular structures and angiogenic cytokines in the bone marrow of iron-deficient rats. The demonstration that angiogenesis may play an important role in secondary thrombocytosis could lead to a new approach in treating symptomatic reactive thrombocytosis by targeting angiogenesis.

Anemia in patients with Covid-19: pathogenesis and clinical significance.

COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (p = 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%, p = 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.

Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders.

The discovery of hepcidin has provided a solid foundation for understanding the mechanisms of systemic iron homeostasis and the aetiologies of iron disorders. Hepcidin assures the balance of circulating and stored iron levels for multiple physiological processes including oxygen transport and erythropoiesis, while limiting the toxicity of excess iron. The liver is the major site where regulatory signals from iron, erythropoietic drive and inflammation are integrated to control hepcidin production. Pathologically, hepcidin dysregulation by genetic inactivation, ineffective erythropoiesis, or inflammation leads to diseases of iron deficiency or overload such as iron-refractory iron-deficiency anaemia, anaemia of inflammation, iron-loading anaemias and hereditary haemochromatosis. In the present review, we discuss recent insights into the molecular mechanisms governing hepcidin regulation, how these pathways are disrupted in iron disorders, and how this knowledge is being used to develop novel diagnostic and therapeutic strategies.

Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: Anemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD. METHODS: Nondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate <60 mL/min/1.73 m2 were included. Logistic regression, multivariate Cox proportional hazards and Poisson regression models adjusted for demographics and comorbidities were used to assess the prevalence and correlates of absolute [transferrin saturation (TSAT) ≤20%, ferritin <100 ng/mL] and functional (TSA T≤20%, ferritin >100-500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization. RESULTS: Of 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12-1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05-1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07-1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1-1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07-1.21)]. Ferritin >500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26-1.51)]. CONCLUSIONS: In a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial.

BACKGROUND: The optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia. METHODS: In this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs). RESULTS: A total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5 mL/min/1.73 m2). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups [0.3% versus 0%; risk difference: 0.29% (95% confidence interval: -0.19; 0.77; P > 0.05)]. Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P = 0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P ≤ 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met. CONCLUSIONS: Compared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.