Transferrin Saturation Index Research Articles

Influence of TMPRSS6 genotype on iron status parameters in stable COPD patients

Background: The SNP rs855791 has been linked to increased hepcidin levels, variations in serum iron, transferrin saturation and red blood cell indices. Our goal was to determine the prevalence of this polymorphism among COPD patients and to assess its impact on iron status parameters including hepcidin in patients with stable COPD. Methods: We analysed iron status parameters and genetic data form 94 COPD patient: 29 patients with wild-type genotype (WT group) and 65 patients with either homozygous or heterozygous genotype (HH group). Additionally, the prevalence of SNP rs855791 was assessed in 192 volunteers. Results: The frequency distribution of SNP rs855791 was comparable between the COPD patients and control subjects (p=0.791). Iron status parameters were within their respective reference values and did not show neither statistically nor clinically significant difference between the WT and HH group of COPD patients. However, after excluding patients with (sub)clinical vitamin B12 deficiency and/or hypoxemia, WT group of patients exhibited significantly lower erythropoietin levels (p=0.015). The area under the curve for EPO was 0.688 (95% CI: 0.545-0.830, p=0.015), with an optimal cut-off of 9.74, sensitivity of 61.2% (95% CI: 58.1-64.3) and specificity of 65.0% (95% CI: 61.8-68.3). Conclusion: In patients with stable COPD, iron status parameters do not differ between WT and HH group of patients. After excluding those with (sub)clinical vitamin B12 deficiency and/or hypoxia, only statistical and not clinical difference in EPO levels was observed suggesting that EPO may regulate hepcidin levels and thus influence the development of iron deficiency and/or anaemia.

Prospective study of restless legs syndrome in a blood donors’ sample

Background and objectivesBlood donation is suggested to increase the risk of Restless Legs Syndrome (RLS). This study aims to assess the prevalence of RLS in Spanish blood donors and determined its potential correlation with iron metabolism parameters. Materials and methodsProspective cohort study of 129 blood donors (54.3% men, 39.44 years ± 11.0) that underwent a physical examination, blood analysis (hemoglobin, ferritin, transferrin saturation index and soluble transferrin receptor) and a RLS screening questionnaire followed by a prospective follow-up study including a clinical phone interview. A multivariate logistic regression model was performed to examine the association between RLS and other variables. ResultsEighty-four (65.1%) participants were repeat blood donors (mean of 2.11 donations/year) at inclusion and 61 (47.4%) at follow-up (mean of 2.09 donations/year). Non-anemic iron deficiency (ferritin < 50 µg/L) was high in women p < 0.001 and in repeat donors (p = 0.003). The prevalence of RLS was 14.1% at inclusion increasing prospectively (19.5%; p = 0.065). On multivariate analysis, gender was the only variable significantly associated with a RLS diagnosis, being higher in women (OR 5.1; 95% CI 1.71-15.3; p = 0.003). ConclusionsDespite the high prevalence of non-anemic iron deficiency there was no association between ferritin, soluble transferrin receptor concentration values and RLS diagnosis. Gender was associated with RLS diagnosis regardless of other variables.

#2907 Characterization of patients needing red blood cell transfusion after kidney transplant

Abstract Background and Aims After kidney transplant there is often need of red blood cell (RBC) transfusion because acute bleeding associated with surgery; or because multifactorial progressive anemization the days after. The aim of this work is to describe the characteristics of transfused kidney transplant recipients (KTR) and compare them to nontransfused controls. Method Retrospective observational study, reviewing the data from electronic medical records of patients receiving a kidney transplant in our hospital during 2022. Results During 2022, 160 kidney transplants were performed in adult people in our hospital and 66 (41.25%) KTR were transfused; some of them receiving the first red blood cell concentration (RBCC) during surgery (19.7%), the rest after surgery hospitalization because acute (10.6%) or progressive (69.7%) anemization. The total number of RBCC received was 1 in the 15% of transfused KTR, 2 in the 48%, 3 in the 8% and ≥ 4CH in the 29%. Among transfused KTR, the 13.6% kidney grafts came from living donors, 48.5% from Maastricht III, 36.4% from brain death and 1.5% from Maastricht II, whereas the kidney grafts of nontransfunded controls came from living donors (11.7%), Maastricht III (54.26%), encephalic death (32.98%) and Maastricht II (1.06%). The mean age of the transfused KTR was 62 years, 63.6% were males, 14.1% with ischemic heart disease, 6.3% with heart failure, moderate-severe valvular heart disease. The 12.12% were treated with acenocoumarol and the 25.7% with acetylsalicylic acid before the transplant hospitalization (whereas in nontransfunded controls the percentages were 10.6% and 21.3% respectively). Haemoglobin (Hb) levels previous to the surgery was lower in transfused KTR, presenting Hb &amp;lt;10 g/dl in the 10.6% of the recipients, whereas in nontransfunded controls was 2.1%. Moreover, ferritin levels were &amp;lt;100 ng/ml in 13.6% and transferrin saturation index was &amp;lt;20% in the 30.3% (whereas in nontransfunded controls it was 25.53% and 38.29% respectively). The mean of Hb before the transplant surgery in transfused KTR was 11.7 ± 1.4 g/dl, and before RBCC transfusion the median was 7.8 g/dl [7.6-8.1]. Conclusion Although more studies are needed, it is interesting to know the characteristics of the KTR that need RBC transfusion in order to asses measures (such us for example, Hb, iron … pretransplant adequate thresholds), in order to avoid if it is possible, unnecessary RBC transfusions.

#2175 Sodium-glucose cotransporter 2 (SGLT2) inhibitors-induced erythropoiesis and cardiovascular events in chronic kidney patients

Abstract Background and Aims Prior research has established that in chronic kidney disease (CKD), elevating hemoglobin (Hb) levels above 11.5 g/dl correlates with heightened thromboembolic event risks and increased mortality. Similar findings are seen in heart failure patients with Hb levels exceeding 13 g/dl, following treatment with erythropoiesis-stimulating agents. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently raise Hb levels in CKD patients, both anemic and non-anemic. This study aims to evaluate the consequences of Hb level elevation due to SGLT2 inhibitors beyond the safe threshold in CKD patients and to investigate its association with cardiovascular (CV) events. Method A retrospective observational study was conducted from January 2016 to December 2021, focusing on CKD patients treated with SGLT2 inhibitors. Patients receiving erythropoiesis-stimulating agents or undergoing renal replacement therapy were excluded. We assessed the impact of Hb level changes on atheroembolic events, blood pressure variations, and mortality, while considering demographic data, red blood cell parameters, and renal function indicators. Patients receiving iron treatment were excluded to ensure accurate ferrokinetic parameter assessment. Results The study included 79 CKD patients, predominantly male (76%) and primarily with type 2 diabetes mellitus (T2DM) as the CKD cause (67%). Average follow-up post-SGLT2 inhibitor initiation was 3.5 years (SD 1.4, 0.7-6.7 years). Hb levels increased mainly in the first six months of treatment, with an average increase of 0.7 g/dl/year from baseline (p &amp;lt; 0.01). Ferritin levels slightly decreased (p 0.002), while the transferrin saturation index remained stable. Baseline estimated glomerular filtration rate (eGFR) did not influence Hb increase. Various responses to SGLT2 inhibitors were noted based on baseline Hb levels. No significant association was found between elevated Hb levels (&amp;gt;16.0 g/dl) and increased atheroembolic events, mortality, or blood pressure changes. However, patients with Hb levels &amp;gt;13.0 g/dl experienced more CV events compared to those maintaining Hb ≤13.0 g/dl, though not statistically significant (0% vs 17.5%: p 0.30). Conclusion SGLT2 inhibitor treatment led to a significant Hb increase unless baseline levels were above 16.0 g/dl. Importantly, elevating Hb levels above 13.0 g/dl appears to be linked with a higher incidence of cardiovascular (CV) events, suggesting a potential risk associated with such an increase in Hb levels in this patient population. This finding underscores the necessity for further research to confirm this correlation and to delineate the safe therapeutic window for Hb levels in CKD patients treated with SGLT2 inhibitors.

ИССЛЕДОВАНИЕ СЕКРЕЦИИ ЭРИТРОПОЭТИНА У БОЛЬНЫХ ВИЧ-ИНФЕКЦИЕЙ С АНЕМИЕЙ ХРОНИЧЕСКИХ ЗАБОЛЕВАНИЙ, ЖЕЛЕЗОДЕФИЦИТНОЙ АНЕМИЙ И СОЧЕТАНИЕМ ДВУХ ТИПОВ АНЕМИЙ

Aim. To compare the secretion of erythropoietin in patients with infection caused by human immune deficiency virus (HIV infection) with anemia of chronic diseases (ACD), iron deficiency anemia (IDA), and their combination. Material and methods. 125 patients with HIV infection were examined: 101 with anemia (55 males, 46 women, 39.4±9.6 years), 24 - a control group of patients with HIV infection without anemia (13 males, 11 women, average age 37.6± 7.37 years). In all patients, the number of red blood cells, the concentration of hemoglobin, ferritin, C-reactive protein (CRP), transferrin saturation index (TSI) and erythropoietin were examined. All patients with anemia after determining TSI, CRP, ferritin based on Van Santen and Worwood criteria were divided into three groups depending on the type of anemia: group 1 - 36 patients with ACD (19 males, 17 women, average age 41.7 ± 11, 8 years, TSI 16.9[IQR, 10.2-23.1]%, ferritin 638.7[IQR, 326-861] μg/l, CRP 54.5 [IQR, 4.8-103.3] mg/l), group 2 – 30 patients with a combination of ACD/IDA (18 males, 12 women, average age 41.2±10 years, TSI 13.2[IQR, 9.8-14]%, ferritin 156.2 [IQR, 123-235] mcg/l, CRP 5.9 [IQR, 0.5-8.2] mg/l), group 3 – 35 patients with IDA (18 males, 17 women, average age 35.4 ±7.1 years, TSI 11.1[IQR, 4.7-13.7]%, ferritin 29[IQR, 4.2-38.9] µg/l, CRP 2.9[IQR, 0.4 -1.6] mg/l). For quantitative indicators, the median (Me), standard error of the mean (m), and interquartile range (IQR) were calculated. The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test. Results. In the ACD group, a lower number of red blood cells was detected (3.3(2.7-3.8)×1012/l), compared to the group of patients with IDA (3.8(3.7-4.1)×1012/l ). Also, in the group of patients with ACD, the maximum concentration of erythropoietin was detected (28.5[11.2-28.5], U/ml), significantly higher than the concentration of this indicator in the ACD/IDA groups (14[8.1-16.3], U/ml), IDA (15.8[6.2-27.4], U/ml) and patients in the control group (6.3[4.9-7.8], U/ml). Conclusions. In the present study, ACD in isolated form or in combination with IDA was diagnosed in 65.3% of patients with HIV infection and anemic syndrome. In patients with ACD, an increased concentration of erythropoietin is combined with the lowest number of red blood cells in comparison with other groups of patients with anemia (p&lt;0.05). The results obtained indicate a compensatory increase in erythropoietin secretion in response to suppressed erythropoiesis, or to reduced sensitivity of erythropoietin receptors. Further study of the importance of erythropoietin in the pathogenesis of chronic disease in patients with HIV infection is necessary, including to improve its treatment.

Evaluation of the influence of pre-analytical factors on serum iron levels, total iron binding capacity, transferrin saturation index and ferritin

Evaluation of the influence of pre-analytical factors on serum iron levels, total iron binding capacity, transferrin saturation index and ferritin

Early improvement of global longitudinal strain after iron deficiency correction in heart failure with reduced ejection fraction.

Iron deficiency correction with ferric carboxymaltose improves symptoms and reduces rehospitalization in patients with reduced left ventricular ejection fraction. The mechanisms underlying these improvements are poorly understood. This study aimed to determine changes in left ventricular contractility after iron treatment as reflected in global longitudinal strain. Prospective single-center study including 43 adults with reduced ejection fraction, non-anemic iron deficiency, and functional class II-III heart failure despite optimal medical treatment. Global longitudinal strain through speckle-tracking echocardiography was measured at baseline and 4weeks after ferric carboxymaltose. A significant improvement in global longitudinal strain was detected (from -12.3%±4.0% at baseline to -15.6%±4.1%, p<.001); ferritin and transferrin saturation index had increased, but ejection fraction presented no significant changes (baseline 35.7%±4.6%, follow-up 37.2%±6.6%, p=.073). In patients with heart failure and reduced ejection fraction, the correction of iron deficiency with ferric carboxymaltose is associated with an early improvement in global longitudinal strain, possibly suggesting a direct effect of iron correction on myocardial contractility.

Intravenous iron for critically ill children. Comparison of three dose regimens.

Anemia is extremely common among patients admitted to pediatric intensive care. Alternative treatments to transfusions such as intravenous iron must be considered. There are no published data for a prospective intravenous (IV) iron study focused in the critically ill children. The objective is to examine the safety and efficacy of intravenous iron sucrose infusion to manage anemia in pediatric critical care. A secondary objective is to examine the effect of different dose regimens of iron sucrose (3, 5, and 7mg/kg dose). Prospective investigation of intravenous iron sucrose utilization at a tertiary pediatric intensive care unit between October 2017 and November 2022. In all 115 patients received a total of 616 infusions of IV iron. Transferrin saturation index (TSI) was the most common altered iron deficiency biomarker (91.8%). After IV iron treatment, hemoglobin showed a significant increase within a 30-day follow-up (9.2 vs. 11.6g/dL, p<.001). There was also a significant improvement in TSI and serum iron (p<.001). Iron deficit replacement was higher in the 7mg/kg dose group (94%) compared to 85.9% in the 5mg/kg regimen and 77.5% in the lower dose group (p=.008), requiring less doses and a shorter time. Very few mild adverse reactions were reported (1.3% of infusions), with no differences between groups. The most frequent adverse effect was gastrointestinal in three cases. There were no anaphylaxis-like or other serious/life-threatening adverse effects. This is the first study to evaluate intravenous iron therapy in pediatric critical care, providing preliminary evidence of safety and efficacy of IV iron sucrose. The 7mg/kg dose regimen showed higher iron deficit replacement in a shorter time, which could be beneficial in critically ill children.

Real-world experience of intravenous iron sucrose supplementation and dynamics of soluble transferrin receptor and hepcidin in a Spanish cohort of absolute iron deficient patients

The study evaluated the safety and effectiveness of the generic intravenous (IV) iron treatment (Feriv®), in a Spanish cohort with absolute iron deficiency (ID) (serum ferritin <50 ng/ml, with or without anaemia) (n = 122; 91% women; median age of 44 years [IQR: 33.7–54]). Iron-related biomarkers were measured before treatment (baseline), 2 weeks after beginning the protocol (intermediate control, IC) and between 7 and 10 days after treatment completion (final time-point). Primary efficacy endpoints were ferritin levels ≥ 50 ng/ml, anaemia restoration or an increase in haemoglobin (Hb) of at least one point in patients without baseline anaemia. After treatment, iron-related biomarkers improved, including ferritin, Hb, sideremia, transferrin, transferrin saturation index, soluble transferrin receptor (sTfR), and hepcidin. Baseline ferritin concentration (13.5 ng/ml [IQR: 8–24.2]) increased at the IC and continued rising at the final time-point, reaching a median ferritin of 222 ng/ml and 97.3% of patients ≥ 50 ng/ml. At the final time-point, anaemia prevalence decreased from 26.2% to 5%, while the 34.1% without baseline anaemia showed an increase in Hb of at least one point. Headache was the only drug-adverse event recorded in 2.3% of patients. At a late time-point (27.5 median weeks after ending therapy [IQR: 22–40]), evaluated in a subgroup of 66 patients, 18% had ferritin levels < 50 ng/ml. Multivariate analysis showed that low baseline ferritin and high sTfR/hepcidin ratio tended to be independently associated with ID recurrence. Feriv® is a safe, effective first-line treatment for absolute ID, with improvement of serum ferritin and Hb. ID recurrence was associated with the baseline degree of iron stores depletion, indicated by serum ferritin, and sTfR/hepcidin ratio.

Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status

BackgroundSome studies have indicated that sodium-glucose cotransporter-2 (SGLT2) inhibitors promote an increase in cell iron use. ObjectivesThe aim of this study was to examine, in patients with stable heart failure with reduced left ventricular ejection fraction (HFrEF), the effect of dapagliflozin on ferrokinetic parameters and whether short-term changes in peak oxygen consumption (Vo2) after dapagliflozin treatment are influenced by baseline and serial ferrokinetic status. MethodsThis was an exploratory analysis of a randomized, double-blind clinical trial that evaluated the effect of dapagliflozin vs placebo on peak Vo2 in patients with HFrEF (NCT04197635) and included 76 of the 90 patients initially enrolled in the trial. Changes in peak Vo2 at 1 and 3 months were explored according to baseline and longitudinal ferrokinetic parameters (natural logarithm [ln] ferritin, transferrin saturation index [TSAT], soluble transferrin receptor, and hepcidin). Linear mixed-effect regression was used for the analyses. ResultsCompared with placebo, dapagliflozin led to a significant decrease in 3-month ln ferritin (P = 0.040) and an increase in 1-month ln soluble transferrin receptor (P = 0.023). Between-treatment comparisons revealed a stepwise increase in peak Vo2 in the dapagliflozin group at 1 and 3 months, which was especially apparent at lower baseline values of TSAT and ferritin (P < 0.05). Lower time-varying values of TSAT (1 and 3 months) also identified patients with greater improvements in peak Vo2. ConclusionsIn patients with stable HFrEF, treatment with dapagliflozin resulted in short-term increases in peak Vo2, which were most marked in patients with surrogates of greater iron deficiency at baseline and during treatment. (Short-Term Effects of Dapagliflozin on Peak Vo2 in HFrEF [DAPA-VO2]; NCT04197635)

Epidemiology and treatment of renal anaemia in Spain: RIKAS retrospective study

Background and objectiveStudies on the prevalence of anaemia in chronic kidney disease in adults not on dialysis (CKD-ND) and in dialysis programmes (CKD-D) in Spain are not recent or focus on certain subgroups. The aim of this study was to know the epidemiology and current treatment patterns of anaemia associated with CKD in Spain. Materials and methodsMulticentre, non-interventional, retrospective study with CKD-ND stage 3a-5 and CKD-D patients treated in Spain between 2015 and 2017 (RIKAS study). ResultsThe prevalence of anaemia in CKD-ND and CKD-D in 2015 was 33.8% and 91.5%, respectively, with similar results during 2016−2017. The prevalence of systemic inflammation in anaemic patients (18.1% and 51.8% for CKD-ND and CKD-D, respectively) was higher, especially in those treated with erythropoiesis-stimulating agents (ESA), compared to the general population with CKD-ND. After 12 months of follow-up, mean ferritin and transferrin saturation index (TSI) values in anaemic patients with CKD-ND were 187.1 ng/mL and 22.2%, respectively, while in CKD-D were 254.6 ng/mL and 20.2%. In ESA-treated patients, mean values were 190.6 ng/mL and 22.0% in ND-CKD, and 255.0 ng/mL and 20.2% in D-CKD. ConclusionsThe prevalence of anaemia and inflammation increased with the disease severity, being higher in D-CKD. Iron parameters in anaemic patients treated or not with ESA are insufficient according to the guidelines, so there is room for improvement in the treatment of anaemia associated with CKD.

#6131 ANEMIA IN PERITONEAL DIALYSIS

Abstract Background and Aims Anemia is one of the most frequent complications of chronic kidney disease (CKD), affects quality of life and increases morbidity and mortality. Prevalence of anemia in patients on peritoneal dialysis (PD) is 83% according to the RIKAS study. Diagnosis of anemia in CKD is set at a hemoglobin (Hb) below 13 g/dL in men and less than 12 g/dL in women. These values serve to define the diagnosis, but not to indicate treatment. Treatment is based on the use of erythropoiesis stimulating agents (ESA) and iron therapy. Absolute iron deficiency (ferritin less than 100 ng/ml and transferrin saturation index (TSAT) less than 20%) and functional iron deficiency (TSAT less than 20% with normal ferritin), require correction with oral or intravenous iron before the use of ESA. Treatment with ESA is indicated when Hb is below 10g/dL despite adequate iron stores. The goal is to achieve Hb values between 10-12g/dL. The aims are evaluating the situation of patients in our PD program with respect to anemia, its prevalence, treatment and its results. Method This is an observational, descriptive, cross-sectional and single-center study. Inclusion criteria were patients older than 18 years with at least 3 months of permanence in our PD program. We collected: age, sex, cause of CKD, type of PD, time on PD, origin (pre-dialysis, hemodialysis, kidney transplant), residual diuresis, diabetes mellitus (DM), high blood pressure (HBP), ischemic heart disease, bleeding, urea, creatinine, albumin, calcium, phosphorus, Hb, hematocrit, iron, ferritin, TSAT, C-reactive protein (CRP), transfusions and treatments (ESA and/or iron therapy). Descriptive statistical analysis (mean, standard deviations, maximums and minimums) and comparative analysis between variables was performed using Chi-square test and ANOVA for qualitative and quantitative variables, respectively. Results N = 58 patients, 64% men and 36% women. The mean age was 61.3+/- 15.54 years. 31% of patients were CKD secondary to glomerulonephritis (predominant etiology). 5% had no cardiovascular risk factors (CVRF), 48% between one and two and 47% more than three. 74% on continuous ambulatory peritoneal dialysis (CAPD). Mean time on dialysis 28.74 +/- 25.05 months. Mean residual diuresis in 24 hours 1199.22 +/- 703.14 cc. Prevalence of anemia 74%. Mean Hb of 10.97 +/-1.29 g/dL with 78% of patients with values between 10-12 g/dl. Mean ferritin of 356.79 +/-226.84 mg/dL with 79% of patients between 100-500 mg/dl. 83% received treatment with ESA, 33% with intravenous iron. No patient received oral iron. 4 patients needed of blood transfusion and 3 of them due to bleeding (2 gastrointestinal bleeding and 1 urinary bleeding). We observed a statistically significant association between higher residual diuresis volume and adequate anemia control (P = .042) and between lower creatinine values and target Hb values (P = .0005). No statistically significant association was observed between adequate anemia control and type of dialysis (p= 0.106), time on dialysis (P = .28), sex (P = .224) and DM (p= 0.139). Conclusion The high prevalence of anemia continues to be a major problem in PD in our program, but similar to other series. Under treatment (ESA and iron therapy) is achieved an adequate control in most patients, although in approximately 20% of patients do not reach the established target. Higher residual diuresis and lower creatinine values (probably due to increased residual renal function) are associated with better anemia control.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ СЕКРЕЦИИ ИНТЕРЛЕЙКИНА-6, ИНТЕРЛЕЙКИНА-1БЕТА, ИНТЕРЛЕЙКИНА-10, ФАКТОРА НЕКРОЗА ОПУХОЛИ-АЛЬФА, ИНТЕРФЕРОНА-ГАММА ПРИ РАЗЛИЧНЫХ ТИПАХ АНЕМИИ У ПАЦИЕНТОВ С ВИЧ-ИНФЕКЦИЕЙ

Aim. To compare the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1-beta, tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) in patients with HIV infection with anemia of chronic disease (ACD), iron deficiency anemia (IDA), as well as their combination. To assess the effect of the studied cytokines on erythropoiesis in each of the studied types of anemia in this category of patients. Material and methods. 125 patients with HIV infection were examined: 101 with anemia (55 men, 46 women, 39.4±9.6 years), 24 patients with HIV infection without anemia (13 men, 11 women, mean age 37.6± 7.37 years). In accordance with the Van Santen and Worwood criteria, by determining the transferrin saturation index (TSI), ferritin concentrations, C-reactive protein (CRP), patients with anemia were divided into 3 groups: group 1 – 36 patients with ACD (19 men, 17 women, mean age 41.7±11.8 years), group 2 – 30 patients with a combination of ACD/IDA (18 men, 12 women, mean age 41.2±10 years), group 3 – 35 patients with IDA (18 men, 17 women, mean age 35.4±7.1 years). In all patients, the number of erythrocytes, the concentration of hemoglobin, ferritin, CRP, CNT, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1beta (IL-1β), interferon-gamma (INF-γ). For quantitative indicators, the arithmetic mean, standard error of the mean, and interquartile range (IQR) were calculated. Significance of differences between several unrelated groups was determined using the Kruskal-Wallis’s test. To assess the relationship between variables, the Spearman correlation coefficient I was calculated. Results. In the ACD group, the maximum concentration of IL-6 (36.6 [IQR, 11.5-51.1]) and IL-10 (21.6 [IQR, 11.4-28.8]) compared with the ACD/IDA group (IL-6 (9.1 [IQR, 5.1-11.4]), IL-10 (15.5 [IQR, (7.1-21.6)]), and IDA (IL- 6 (6.2 [IQR, 1.6–7.2]), IL-10 (8.6 [IQR, 3.9–9.3]) (p&lt;0.05). In the groups of patients with ACD and ACD/IDA, the maximum and almost equal concentrations of TNF-α (15.2 [IQR,6.1-24.1] in the ACD group and 17.3[IQR,7.9-17.3] in the ACD/IDA group), IL-1β (16.7[IQR,4.7-28.9] in the ACD group and 19.2 [IQR,3.9-28.8] in the ACD/IDA group), INF-γ ( 62.6[IQR,4.6-85.3] in the ACD group and 58.3[IQR,8.5-37.5] in the ACD/IDA group), which were statistically significantly higher than the concentrations of these cytokines in patients with IDA and the control group. There were no significant differences in the concentrations of TNF-α, IL-1β, IL-10 and IFN-γ between patients with IDA and the control group. Significant moderate and strong negative correlations were found in the groups of patients with ACD and ACD/IDA between all studied cytokines, erythrocytes and hemoglobin. In the IDA group, the correlation coefficients between cytokines, erythrocytes, and hemoglobin are low or absent. Conclusions. In patients with HIV infection, a wide prevalence of ACD has been shown, especially in patients with immunodeficiency and in the late stages of the disease. ACD, unlike IDA, has a complex multicomponent pathogenesis. This study shows the importance of pro-inflammatory and inflammatory cytokines in the development of ACD in HIV patients, including due to their negative effect on erythropoiesis and hemoglobin synthesis. A working version of the classification of ACD (with a predominant iron deficiency, with impaired regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin) has been proposed. It is necessary to further study the pathogenesis of ACD in this category of patients to improve treatment.

Reticulocyte Hemoglobin Equivalent has Comparable Predictive Accuracy as Conventional Serum Iron Indices for Predicting Iron Deficiency and Anemia in a Nonhuman Primate model of Infantile Iron Deficiency

BackgroundInfantile iron deficiency (ID) causes anemia and compromises neurodevelopment. Current screening relies on hemoglobin (Hgb) determination at 1 year of age, which lacks sensitivity and specificity for timely detection of infantile ID. Low reticulocyte Hgb equivalent (RET-He) indicates ID, but its predictive accuracy relative to conventional serum iron indices is unknown. ObjectivesThe objective was to compare diagnostic accuracies of iron indices, red blood cell (RBC) indices, and RET-He for predicting the risk of ID and IDA in a nonhuman primate model of infantile ID. MethodsSerum iron, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation (TSAT), Hgb, RET-He, and other RBC indices were determined at 2 wk and 2, 4, and 6 mo in breastfed male and female rhesus infants (N = 54). The diagnostic accuracies of RET-He, iron, and RBC indices for predicting the development of ID (TSAT < 20%) and IDA (Hgb < 10 g/dL + TSAT < 20%) were determined using t tests, area under the receiver operating characteristic curve (AUC) analysis, and multiple regression models. ResultsTwenty-three (42.6%) infants developed ID and 16 (29.6%) progressed to IDA. All 4 iron indices and RET-He, but not Hgb or RBC indices, predicted future risk of ID and IDA (P < 0.001). The predictive accuracy of RET-He (AUC = 0.78, SE = 0.07; P = 0.003) for IDA was comparable to that of the iron indices (AUC = 0.77–0.83, SE = 0.07; P ≤ 0.002). A RET-He threshold of 25.5 pg strongly correlated with TSAT < 20% and correctly predicted IDA in 10 of 16 infants (sensitivity: 62.5%) and falsely predicted possibility of IDA in only 4 of 38 unaffected infants (specificity: 89.5%). ConclusionsRET-He is a biomarker of impending ID/IDA in rhesus infants and can be used as a hematological parameter to screen for infantile ID.

Influence of Nutritional Parameters on the Evolution, Severity and Prognosis of Critically Ill Patients with COVID-19.

This study evaluated the clinical and nutritional status, the evolution over three days, and the relationship between nutritional, inflammatory, and clinical parameters of critically ill patients with COVID-19. A longitudinal study was conducted in the Intensive Care Unit of the Virgen de las Nieves University Hospital in Granada (Spain). The study population comprised patients with a positive polymerase chain reaction test for COVID-19 presenting critical clinical involvement. Clinical outcomes were collected, and inflammatory and nutritional parameters (albumin, prealbumin, transferrin, transferrin saturation index, cholesterol, triglycerides and Controlling Nutritional Status (CONUT) score) were determined. A total of 202 critical patients with COVID-19 were selected, presenting highly altered clinical-nutritional parameters. The evolution experienced by the patients on the third day of admission was a decrease in albumin (p &lt; 0.001) and an increase in prealbumin (p &lt; 0.001), transferrin (p &lt; 0.002), transferrin saturation index (p &lt; 0.018), and cholesterol (p &lt; 0.001). Low levels of albumin, prealbumin (on the third day) and high CONUT score (on the third day) showed an association with higher mortality. Nutritional variables were inversely correlated with clinical and inflammatory parameters. Critically ill patients with COVID-19 have poor nutritional status related to a poor prognosis of disease severity and mortality.

Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients.

Iron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART. In this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm3 (N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman's rho correlation coefficient. We selected samples from HIV-infected subjects (aged 42[34-47], 95% males), young age-matched (aged 40[30-58], 60% males), and elderly controls (aged 82[78-88], 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young, r=-0.587, p=0.002; Elderly, r=-0.496, p=0.012) or transferrin saturation index (Young, r=-0.581, p=0.002; Elderly, r=-0.489, p=0.013) were negative in both controls while positive in HIV (r=0.464, p<0.0001 and r=0.421, p<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young, r=-0.533, p=0.006; Elderly, r=-0.473, p=0.017), was absent in HIV (r=0.082; p=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 42[32-51], 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV. Virologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.

Single shot of intravenous iron in cardiac surgery: The ICARUS study

BackgroundIron deficiency (ID), with or without anemia, is commonly observed among patients scheduled for cardiac surgery. We investigated if screening ID in the immediate preoperative period and treating ID patients regardless of anemia could reduce perioperative transfusion requirements. MethodsThis is an observational single-center propensity score-matched study including candidates to elective cardiac surgery prospectively and retrospectively enrolled. Prospectively enrolled patients were screened for ID at hospital admission: if ferritin was ≤100 μg/L or ≤ 300 μg/L with transferrin saturation index ≤20% they received intravenous ferric carboxymaltose, B12-vitamin, and folic acid. A retrospective series of patients not screened for ID and matched for gender, type of surgery, BMI, Goudie transfusion risk score, hemoglobin level, and red blood cell (RBC) indices, served as controls. The primary outcome was the proportion of patients requiring ≤1 packed RBC (pRBC) unit within day 7 or discharge The main secondary outcomes were intraoperative and postoperative pRBC transfusions, duration of hospitalization, and cost-effectiveness of ID screening and treatment. ResultsWe included 479 prospective and 833 retrospective cases: 442 patients screened for ID and 442 matched controls with unknown iron status were analyzed. ID was observed in 196 patients (44.3%) and iron was administered 1 day (IQR 1–2) before surgery. Overall, 76.9% of patients in the prospective group and 69.7% of controls received ≤1 pRBC transfusion (p = 0.014). The risk for multiple transfusions was lower in patients screened for ID (OR 0.689, 95% CI 0.510–0.930). Despite similar Hb levels at day 7, patients in the prospective group received fewer postoperative pRBC transfusions (p < 0.001) and had a shorter hospital length of stay (p < 0.001). Globally, hospitalization costs were lower in patients screened and treated for ID. ConclusionsShort-term pre-operative iron therapy is associated with a reduction in postoperative transfusions in anemic and non-anemic ID cardiac surgery patients and has a favorable impact on hospitalization costs. Clinical trial registrationNCT04744181

Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease.

Patients with chronic kidney disease (CKD) develop anemia largely because of inappropriately low erythropoietin (EPO) production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open‐label, clinical trials in dialysis‐dependent and non–dialysis‐dependent patients with CKD and anemia, the hypoxia‐inducible factor prolyl hydroxylase inhibitor, vadadustat, was noninferior to the erythropoiesis‐stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum EPO, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. Achieved hemoglobin concentrations were similar in patients treated with either vadadustat or darbepoetin alfa, but compared with patients receiving darbepoetin alfa, those receiving vadadustat had erythrocytes with increased mean corpuscular volume and mean corpuscular hemoglobin, while the red cell distribution width was decreased. Increased serum transferrin concentrations, as measured by total iron‐binding capacity, combined with stable serum iron concentrations, resulted in decreased transferrin saturation in patients randomized to vadadustat compared with patients randomized to darbepoetin alfa. The decreases in transferrin saturation were associated with relatively greater declines in serum hepcidin and ferritin in patients receiving vadadustat compared with those receiving darbepoetin alfa. These results for serum transferrin saturation, hepcidin, ferritin, and erythrocyte indices were consistent with improved iron availability in the patients receiving vadadustat. Thus, overall, vadadustat had beneficial effects on three aspects of erythropoiesis in patients with anemia associated with CKD: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.

PB2246: FEATURES OF THE SECRETION OF HEPCIDIN, A SOLUBLE TRANSFERRIN RECEPTOR DEPENDING ON THE TYPE OF ANEMIA IN PATIENTS WITH MALIGNANT NEOPLASMS

Background: Anaemia of chronic disease or anaemia of chronic inflammation is the most common cause of anaemia in admitted patients. This anemia can be a consequence of several states such as malignancies, chronic infections and auto-immune diseases, thereby indicating the multiplicity in pathogenetic pathways. Aims: to study the secretion of hepcidin a soluble transferrin receptor (sTfR) in patients with malignant neoplasms with anemia of chronic diseases (ACD), iron deficiency anemia (IDA) and an ACD/IDA combination and to investigate their effect on the development of anemia Methods: 106 patients with stage II-IV of solid malignant neoplasms were examined: 84 with anemia (55 men, 29 women, 67.1±9.9 year olds), 22 without anemia (17 men, 5 women, 60.2±14.9 year olds). According to Van Santen and Worwood criteria, by determining the transferrin saturation index (TSI), ferritin, C-reactive protein (CRP), patients were divided into 4 groups: group 1 - ACD, 31 (20/11 patients (hemoglobin 99.2[IQR,87-118], erythrocytes 3.5[IQR,3.1-3.9], TSI 19.9[IQR,12.6-22], ferritin 443.4[IQR,361.9-574.9], CRP 137.1[IQR,89.7-155.2]), group 2 – ACD/IDA, 28 (18/10) patients (hemoglobin 111[IQR,91-128], erythrocytes 4.02[IQR,3.3-4.5], TSI 12.7[IQR,7.4-20.5], ferritin 220.5[IQR,102.7-370.6], CRP 53.4[IQR,14.5-64.5]), group 3 - IDA, 25(17/8) patients (hemoglobin 107 [IQR,96.5-121.5], erythrocytes 4.1[IQR,3.7-4.5], TSI 7.3[IQR,4.2-12.5], ferritin 19.3[IQR,10-24.1], CRP 14[IQR,6.6-23.9]), group 4(control) - 22 patients without anemia (hemoglobin 135.3[IQR,125-150], erythrocytes 4.4[IQR,3.9-4.9], TSI 16.8[IQR,12.4-21.6], ferritin 111[IQR,25.7-189.2], CRP 11.4[IQR,3.3-16.8]). The significance of differences between several unrelated groups was determined using the Kruskal-Wallis test at a significance level (p) of less than 0.05. To assess the relationship between the variables, the Spearman correlation coefficient (r) was calculated. Results: the ACD group had the highest concentrations of CRP, ferritin in comparison with the other groups (p<0.05). The TSI in the ACD group was higher compared to the IDA and ACD/IDA groups (p<0.05), and did not differ from the control group (p>0.05). The ACD group had the maximum concentration of hepcidin (47.3[IQR,29.7-60.5]) compared with the ACD/IDA group (34.6[IQR, 26.6-50]) (p<0.05), the IDA group (6.16[IQR,1.8-10]) (p<0.05) and the control group (23.5[IQR,4.7-45.4) (p<0.05). The concentration of sTfR in patients with anemia did not differ (p>0.05) and amounted to 26.1[IQR,19.8-28.3] in ACD, 23[IQR,13.3-21.1] in ACD/IDA, 28.4[IQR,16.1-34.4] in IDA, 16.8[IQR,13.7-18.8] in the control group. In all groups with anemia, the concentration of sTfR was higher compared to the control group (p<0.05). A correlation was found between the number of erythrocytes and the concentration of hepcidin (r=-0.57), as well as between the concentration of hemoglobin and sTfR (r=-0.57). Summary/Conclusion: Patients with solid malignancies may have IDA, ACD, or a combination of both. The high concentration of hepcidin in patients with ACD, the presence of a correlation between it and erythrocytes confirms its importance in the development of anemia and the possibility of using it for the diagnosis of ACD. The absence of differences in the concentration of sTfR between patients of the three groups with anemia indicates a low value of this indicator for the differential diagnosis of ACD and IDA. The correlation between sTfR and hemoglobin reflects the importance of sTfR in the pathogenesis of anemia in cancer patients.

Influence of Elective Cesarean Calving (with and without Dexamethasone Induction) on the Erythrogram and Iron Serum Profiles in Nellore Calves.

Simple SummaryThe use of elective cesarean section has become common practice in double muscled breeds of in vitro fertilized cattle and cloned calves, particularly before the onset of labor, when it is known that cesarean section negatively affects neonatal respiration and metabolic adaptation in humans and calves. However, there is a lack of information on the effects of cesarean section on the erythrogram of calves. The objectives of this study are to characterize the hematological profile of Nellore calves born spontaneously or by elective C-section (with or without induction with dexamethasone) and to verify the frequency of anemia in these animals. Our data indicate that in the first day of life there was a decrease in the number of red blood cells, hemoglobin rates, and values of the globular volume regardless of the type of birth; however, the recovery of these hematological values happened faster in zebu calves born spontaneously than in the group born by elective C-section (with or without induction). The results suggest that iron supplementation in the first month of life in Nellore calves that underwent cesarean section could be recommended to prevent the iron deficiency anemia observed in this study.The aim of the present study is to evaluate the erythrogram and iron serum profiles of neonatal calves born spontaneously or born by elective cesarean section with or without dexamethasone induction. The research was performed on 38 newborn Nellore calves. Three groups of calves were assigned according to the type of birth: calves born by spontaneous vaginal calving (n = 10), calves born by elective cesarean section without inducing labor (n = 14), and calves born by elective cesarean section with labor induction with dexamethasone (n = 14). Blood samples to assess red blood cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), concentration of mean corpuscular hemoglobin (MCHC), serum iron (SFe), total capacity to bind iron to transferrin (TIBIC), and transferrin saturation index (TSI) were performed at calving (0, 3, 6, and 12 h of life) and on 1, 2, 3, 5, 7, 10, 15, and 30 days of life. Regardless of the experimental group (calves born spontaneously, or born by elective cesarean section with or without dexamethasone induction), in the first day of life there was a decrease in the number of red blood cells, hemoglobin rates, and values of the globular volume. In the period of the first 10 days of life, animals from spontaneous vaginal delivery quickly recovered values of erythrocytes, hemoglobin, and packed cell volume, whereas animals born by elective C-section (induced and uninduced) did not recover as quickly in their rates of hemoglobin and packed cell volume values. In calves born by elective C-section (induced and uninduced), it was observed in their period between 10 and 30 days of life that the MCV and MCH were reduced by passing the presenting microcytic hypochromic when compared with calves obtained by spontaneous vaginal delivery. In the period between 10 and 30 days of life, the levels of SFe and TSI in animals born by elective C-section (induced and uninduced) are significantly lower. The differences in the erythrogram values between Nellore calves born spontaneously and those by elective C-section with or without induction must be considered consequent to the process of neonatal adaptation to extrauterine life. Iron supplementation in the first month of life in calves from cesarean could be recommended to prevent anemia of this iron deficiency.