Changes In Hb Research Articles

A multifaceted approach to investigate interactions of thifluzamide with haemoglobin

This study explores the interaction between the pesticide thifluzamide (TF) and haemoglobin (Hb) to understand potential structural changes that might affect Hb's function. Using a combination of UV–visible and fluorescence spectroscopy, circular dichroism (CD), molecular docking, molecular dynamics (MD) simulations, and electrochemical methods, we investigated these interactions in detail. Spectroscopy results indicated the formation of a stable TF-Hb complex, with a binding constant of 6.64 × 105 M−1 at 298 K and a 1:1 binding ratio. The stability of this complex was confirmed by a free energy change (∆G) of −34.491 kJ mol−1. CD spectroscopy was employed to confirm structural changes in Hb due to thifluzamide binding. Molecular docking studies revealed that TF interacts with specific amino acids in Hb, such as ALA, HIS, VAL, LYS, and LEU, with a binding energy of −25.10 kJ mol−1. MD simulations supported these findings by showing conformational changes in Hb upon TF binding, as indicated by RMSD and RMSF analyses. Electrochemical experiments further confirmed the interaction, evidenced by a consistent decrease in the TF peak in the presence of Hb. Overall, our findings shed light on how TF binds to Hb, causing structural changes that could potentially impact its normal function. This research enhances our understanding of the biochemical effects of TF on Hb, which could have significant implications for biological systems.

Hemoglobin targeting potential of aminocarb pesticide: Investigation into dynamics, conformational stability, and energetics in solvent environment

Aminocarb (AMC), a carbamate pesticide, due to its prevalent usage exhibits increased accumulation in the environment affecting both insects and humans. It enters the human body via food grains and be transported through bloodstream. AMC's chemical structure, containing specific molecular frameworks and functional groups, enables it to bind with proteins like albumin and hemoglobin. Given that molecules with similar architecture are known to bind with hemoglobin, we aimed to explore Aminocarb's binding capability and the potential mechanism or mode of its interaction with hemoglobin. Hb being a tetramer with a profound interface between amino acid chains offers multiple binding sites. It is therefore important to investigate the structural aspects of binding of AMC by employing various spectroscopic and in-silico methods. The surface of the α1 chain near the α1β2 interface emerges as the preferred binding site for AMC, primarily due to its conformational restrictions. In its bound state, AMC tends to maintain a relaxed conformation, closely resembling its globally optimized geometry, and resides in close proximity to the α1 chain via multiple hydrophobic contacts and water bridge as observed in molecular dynamics (MD) simulations. Fluorescence quenching experiments showed moderate binding strength (7.7 × 10⁴ L M⁻1 at 288 K, 7.8 × 10⁴ L M⁻1 at 298 K, 7.9 × 10⁴ L M⁻1 at 308 K) and spontaneous binding, driven by hydrophobic and van der Waals interactions, as indicated by enthalpy (0.80–0.91 kJ mol⁻1), entropy (0.0970–0.0974 kJ mol⁻1), and Gibbs free energy (−27.13 to - 29.08 kJ mol⁻1). Circular dichroism experiments reveal no major structural changes in Hb. Quantum chemical calculations and MD simulations reveal conformation-dependent energy differences, enhancing our understanding of AMC's binding mechanism to Hb.

Daily versus Alternate-Day Iron Supplementation for Pregnant Women with Iron Deficiency Anemia: A Randomized Controlled Trial.

This study aimed to evaluate the most effective regimen to raise hemoglobin (Hb) by comparing alternate-day dosing of iron to daily dosing in pregnant women with iron deficiency anemia. Women with Hb < 11.0 g/dL and ferritin ≤ 25 µg/L between 120/7 and 340/7 weeks' gestation were recruited. A total of 88 patients were randomized using block randomization with 1:1 allocation to receive either 1 tablet of 325 mg ferrous sulfate on consecutive days or 2 tablets every other day. The primary outcome, the change in Hb after 6 weeks of treatment was assessed using an analysis of covariance to adjust for baseline level. Secondary outcomes included change in ferritin, hepcidin, side effects, and compliance. Patients completed a questionnaire to assess for adverse symptoms and adherence was monitored by installing a pill reminder app on smartphones of patients. A total of 88 patients were consented. The daily iron group had a greater proportion of nulliparous women (40 vs. 7%). Most patients (98%) had mild anemia (Hb: 9-10.9 g/dL) at recruitment, with a median gestational age of 28.1 weeks (interquartile range [IQR]: 25.6, 30.9) and median duration of treatment of 42 days (IQR: 35, 45). At 6 weeks, the daily iron group had a mean increase in Hb of 0.8 ± 0.9 g/dL, whereas the alternate-day iron group had a mean increase of 0.5 ± 1.0 g/dL (baseline adjusted difference of means: -0.3 [95% confidence interval: -0.7, 0.1], p = 0.15). Frequency of adverse effects attributable to iron were similar between groups. Patient self-reported compliance to treatment was also similar between groups. Among those that used the app, compliance was higher among the daily group compared with the alternate daily group (median: 95.5% [IQR: 75, 100] vs. 85% [IQR: 40, 92]), although this difference was not statistically significant (p = 0.07). This trial suggests that there are no significant differences between alternate-day iron supplementation and daily iron supplementation for treating iron deficiency anemia. · Intermittent iron provides no additional benefit compared to daily iron in the treatment of anemia.. · Patient compliance to treatment was similar between the groups.. · The frequency of side effects was not significantly different between the groups..

Research on performance variations of different asphalt binders results from microwave heating during freeze-thaw cycles

Microwave heating (MH) as a sustainable pavement maintenance method can effectively repair the cracks caused by freeze-thaw (FT) damage. However, binders' properties may be weakened during this process then reduces the pavement life. For this purpose, this work aims to investigate the performance changes of neat binders (Nb) and high-viscous binders (Hb) during FT and MH. The physicochemical, rheological, and deformation properties are investigated after FT and MH. Results indicate that asphalt binders become harder and lead to an increase in carbonyl index (CI) and sulfoxide index (SI) after FT. MH has a limited damage level for binders especially for Hb, causing a slight increase in CI and SI, compared to binders after FT. Polymers play an important role in the viscoelastic responses of asphalt binders. Changes in viscoelastic properties of Nb mainly result from the binder damage of FT and MH, while viscoelastic changes of Hb are mainly due to the damage of polymers. This different damage mechanism causes Hb to show better resistance compared to Nb, which is reflected in modulus and phase angle. BBR tests indicate that MH can further deteriorate the damage of both binders, but Hb shows a lower performance decline compared to Nb, and it is recommended to conduct MH at the region with a minimum temperature above −12 °C. MSCR results reveal that FT and MH can improve the rutting resistance of Nb due to the hardening phenomenon after damage, and reduce the elastic stability of Hb due to the damage to polymers. In summary, Nb is sensitive to MH, its performance can be further damaged after MH. Hb has better resistance to MH, its properties do not further deteriorate, so Hb is more applicable to MH.

Study on the Effects of Acupuncture with the "Yizhi Tiaoshen" Acupoint Formula on Blood Oxygen Metabolism and Neural Function in Key Brain Regions of AD Rats.

Exploring the effects of acupuncture at the "Yizhi Tiaoshen" acupoint on blood oxygen metabolism and neurological function changes in the brain regions of AD model rats. The AD model was replicated by intraperitoneal injection of D-galactose combined with bilateral hippocampal CA1 injection of Okadaic acid (OA). Thirty rats with successfully replicated model were selected through Morris water maze experiment and randomly divided into model group, donepezil hydrochloride group, and acupuncture group, with 10 rats in each group. After treatment, fNIRs were used to detect changes in Oxy Hb, Deoxy Hb, and Total Hb in the cerebral cortex of rats in each group, in order to evaluate the neurological function changes in key brain areas. The escape latency of the donepezil hydrochloride group and the acupuncture group was shortened, the number of crossings through the original platform increased, and the duration of stay in the quadrant where the original platform was located was prolonged. Based on fNIRs detection, the main differential channels of blood oxygen metabolism in AD rats were identified as 2-2 and 8-7, corresponding to the prefrontal and parietal lobes, respectively. The concentrations of Oxy Hb and Total Hb were significantly increased in both treatment groups, while the concentration of Deoxy Hb was significantly decreased. Acupuncture with the "Yizhi Tiaoshen" acupoint formula and donepezil hydrochloride can improve the learning and memory function of AD rats, and its mechanism may be related to improving blood oxygen metabolism in the prefrontal and parietal regions and protecting neuronal function.

Less inflammatory response in the direct anterior than in the direct lateral approach in patients with femoral neck fractures receiving a total hip arthroplasty: exploratory results from a randomized controlled trial.

It is still debatable which is the least invasive approach to the hip joint in arthroplasty for a femoral neck fracture (FNF). We compared the traditional direct lateral approach (DLA) with the direct anterior approach (DAA) regarding creatine kinase (CK), C-reactive protein (CRP), and hemoglobin (Hb). In a randomized controlled trial, 130 elderly patients with dislocated FNFs treated with total hip arthroplasty (THA) were included. CK, CRP, and Hb were measured preoperatively and on postoperative days 1 to 4 and were compared between the DAA and DLA groups using repeated measures mixed-effect models. The CK level was significantly higher on the 1st postoperative day in the DLA group, 597 U/L (95% confidence interval [CI] 529-666) vs 461 U/L (CI 389-532), estimated mean difference (MD) 136 U/L (CI 38-235). The CRP levels were significantly higher on postoperative days 3 and 4 in the DLA group, 207 mg/L (CI 189-226) vs 161 mg/L (CI 143-180), estimated MD 46 mg/L (CI 19-72) and 162 mg/L (CI 144-181) vs 121 (CI 102-140), estimated MD 41 mg/L (CI 15-68). Blood loss, expressed as difference in Hb, did not differ between the groups. In an elderly population with FNFs, we found that the DAA, compared with the DLA, results in less CK and CRP increase, but no change in Hb.

Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry.

Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from discharge to 1year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria. First, 547 HFpEF cases were divided into two groups, Hb<11.0g/dL (n=218) and Hb≥11.0g/dL (n=329), according to Hb at discharge, and further were divided according to Hb 1year after discharge into Hb<11.0g/dL (G1, n=113), Hb≥11.0g/dL (G2, n=105), Hb<11.0g/dL (G3, n=66), and Hb≥11.0g/dL (G4, n=263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curve that predicts MACE. We examined the incidence rate of MACE between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb. In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb≥11.0g/dL to <11.0g/dL than G4 with persistently Hb≥11g/dL (adjusted hazard ratio (HR): 3.14 [95% confidence interval (CI), 1.76-5.60], P<0.001). MACE was not significantly different between G2 with improving anaemia from Hb<11.0g/dL to ≥ 11.0g/dL and G4 (adjusted HR: 1.37 [95% CI, 0.68-2.75], P=0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronic obstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR: 1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). In multivariate linear regression analysis, covarying factors with change in Hb were BMI (β=-0.098), serum albumin (β=0.411), and total cholesterol (β=0.179). Change in haemoglobin after discharge using a lower cut-off value than WHO criteria has prognostic impact in patients with HFpEF.

TEMPORARY REMOVAL: Drivers of Anemia Reduction among Women of Reproductive Age in Senegal: A Country Case Study

BackgroundIn Senegal, anemia prevalence among women of reproductive age (WRA) decreased from 59% in 2005 to 54% in 2017. However, determinants of reduction in disease burden under challenging public health conditions have not been studied. ObjectiveTo conduct a systematic in-depth assessment of the quantitative and qualitative determinants of anemia reduction among WRA in Senegal between 2005 and 2017. MethodsStandard Exemplars in Global Health methodology was used for quantitative analyses using Senegal’s Demographic and Health Surveys. Qualitative analyses included a systematic literature review, program/policy analysis, and interviews with key stakeholders. A final Oaxaca-Blinder decomposition analysis (OBDA) evaluated the relative contribution of direct and indirect factors. ResultsAmong non-pregnant women (NPW), mean hemoglobin (Hb) increased from 11.4 g/dL in 2005 to 11.7 g/dL in 2017 (p<0.0001), corresponding to a 5%-point decline in anemia prevalence (58% to 53%). However, inequities by geographical region, household wealth, women’s educational attainment, urban compared to rural residence, and antenatal care (ANC) during last pregnancy continue to persist. During this time period, several indirect nutrition programs were implemented, with stakeholders acknowledging the importance of these programs, but agreeing there needs to be more consistency, evaluation, and oversight for them to be effective. Our OBDA explained 59% of the observed change in mean Hb, with family planning (25%), malaria prevention programs (17%), use of iron and folic acid (IFA) during last pregnancy (17%), and improvement in women’s empowerment (12%) emerging as drivers of anemia decline, corroborating our qualitative and policy analyses. ConclusionsDespite a reduction in anemia prevalence, anemia remains a severe public health problem in Senegal. To protect the gains achieved to date, as well as accelerate reduction in WRA anemia burden, focused efforts to reduce gender and social disparities, and improve coverage of health services, such as family planning, IFA, and antimalarial programs, are needed.

TEMPORARY REMOVAL: Drivers of Anemia Reduction among Women of Reproductive Age in the Philippines: A Country Case Study

BackgroundAnemia prevalence among women of reproductive age (WRA) in the Philippines was 25% in 2000, decreasing to 13% in 2018. To date, an in-depth assessment of the determinants associated with this decline has not been conducted. ObjectiveTo conduct a systematic in-depth assessment of the quantitative and qualitative determinants of anemia among WRA in the Philippines between 2008 and 2018. MethodsEmploying standard Exemplars methodology, we conducted quantitative analyses using the Philippines’ National Nutrition Survey, the Expanded National Nutrition Survey, and the Philippines National Demographic and Health Surveys. Qualitative analyses included a comprehnsive literature review, program/policy analysis, and interviews with stakeholders to understand country-level enablers and barriers to WRA anemia decline in the Philippines. A final Oaxaca-Blinder decomposition analysis (OBDA) evaluated the relative contribution of direct and indirect factors. ResultsAmong non-pregnant women (NPW), mean hemoglobin (Hb) increased from 12.7 g/dL in 2008 to 13.1 g/dL in 2018 (p<0.01), corresponding to an 11%-point decline in anemia prevalence (23% to 12%). Inequities by geographical region, household wealth, and women’s educational attainment narrowed considerably during this time. Important direct and indirect nutrition programs were introduced during our study period, including universal healthcare and food fortification. Country experts interviewed credited programs focused on alleviating micronutrient deficiencies and poverty, and improvements in women’s health and well-being, for the country's extraordinary success. OBDA explained ∼50% of the observed change in mean Hb among NPW, with family planning (35%), household socio-demographics (29%), and improvement in women’s nutrition (23%) emerging as critical drivers of anemia decline, corroborating our qualitative and policy analyses. ConclusionsTo protect these gains, WRA anemia prevention efforts in the Philippines should continue to focus on universal healthcare access, women’s empowerment, and poverty alleviation.

#2898 Exposure response model describing hematologic changes with chronic treatment of CKD anemia with vadadustat

Abstract Background and Aims Vadadustat (VADA) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate endogenous erythropoietin production, increasing iron mobilization and red blood cell production. VADA is approved in 36 countries globally and is indicated in the European Union for the treatment of symptomatic anaemia associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis and is an alternative to treatment with erythropoiesis-stimulating agents (ESAs). The aim of this work was to develop a predictive, semi-mechanistic model to understand the effects of VADA and erythropoiesis-stimulating agents (ESAs) on hemoglobin response and to evaluate the impact of intrinsic and extrinsic patient characteristics on that response for non-dialysis dependent (NDD) and dialysis-dependent (DD) patient populations. Method A predictive semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for VADA and ESA treatment was developed using nonlinear mixed effects methods. The model describes changes in reticulocyte count (RETICs), mature erythrocytes (RBCs) and hemoglobin (Hb) as a function of drug exposure and subject-specific characteristics. The dataset was based on data from 7 Phase 1 to Phase 3 studies (Table 1; N = 894 for VADA; N = 560 for ESA modeling) in healthy volunteers and subjects with NDD- or DD-CKD who were either ESA-naïve or ESA experienced but not receiving treatment at screening. Prior population PK modeling of VADA provided estimated drug exposures for VADA-treated subjects, while dose normalized to standard units (IU/kg/wk) was used as the exposure metric for subjects on ESA. Each of these exposure metrics could vary with time, as the dose was adjusted according to observed Hb response. This work evaluated alternative model structures, as well as covariate effects affecting Hb individual response. Results A predictive semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for VADA and ESA treatment was developed using nonlinear mixed effects methods. The model describes changes in reticulocyte count (RETICs), mature erythrocytes (RBCs) and hemoglobin (Hb) as a function of drug exposure and subject-specific characteristics. The dataset was based on data from 7 Phase 1 to Phase 3 studies (Table 1; N = 894 for VADA; N = 560 for ESA modeling) in healthy volunteers and subjects with NDD- or DD-CKD who were either ESA-naïve or ESA experienced but not receiving treatment at screening. Prior population PK modeling of VADA provided estimated drug exposures for VADA-treated subjects, while dose normalized to standard units (IU/kg/wk) was used as the exposure metric for subjects on ESA. Each of these exposure metrics could vary with time, as the dose was adjusted according to observed Hb response. This work evaluated alternative model structures, as well as covariate effects affecting Hb individual response. A similar model structure was found to describe early changes in RETICs and longer-term changes in Hb for both VADA and ESAs. In each case, the magnitude of response increases with increased drug exposure up to a maximum value (Emax), and the Emax values were similar between VADA and ESAs. Subject intrinsic predictors of response included eGFR, subject age, BMI, and serum albumin, while extrinsic factors affecting response included geographic region, limits on acceptable Hb values (which also differ by geographic region) and the presence of previous ESA treatment. Interestingly, Hb responses were also correlated with changes in serum hepcidin, a key regulator of iron homeostasis, following both VADA and ESA treatment. Differences between the response to VADA and ESA were also described, including differences in temporal changes in RETICs and Hb. Conclusion This model showed an exposure-response relationship between VADA or ESA treatment and changes in RETICs and Hb for ESA naïve or ESA-experienced CKD subjects. The model will be used to inform dosage recommendations for VADA based on patient characteristics.

#708 Retrospective analysis of the real-world experience of desidustat in the treatment of chronic kidney disease induced anemia

Abstract Background and Aims Chronic kidney disease (CKD) is commonly associated with an increased risk of anemia, which significantly impacts patients' quality of life and increases morbidity and mortality. Current treatment options for anemia in CKD, such as injectable erythropoiesis-stimulating agents (ESAs) have limitations and safety concerns. Desidustat, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) has shown promise in stimulating endogenous erythropoiesis and addressing anemia in CKD. Therefore, the present study assesses the real-world clinical efficacy and safety of the desidustat treatment for a short duration of 6 months (24 weeks) in CKD patients with anemia. Method This is a retrospective analysis of 140 patients at our center who received Desidustat as a treatment for CKD anemia. Desidustat was initiated in all patients at 100 mg three times a week. Dose adjustment was done every 4 weeks as per the Hb level of the patient. The duration of the study was 6 months. The primary endpoint of the present study was a change in Hb from baseline with desidustat therapy and the secondary endpoint was safety of the treatment. Results The majority of the patients were Pre-dialysis 74.28% (n = 104) and 25.72% (n = 36) were dialysis-dependent patients. Of 36 dialysis-dependent patients; 75% (n = 27) were on dialysis three times a week, rest were on twice-a-week dialysis. In the current study, the majority of patients had Hypertension (95.7%) and diabetes (68.57%) as co-morbidities. All the patients in the current study were maintained with 100 mg Desidustat, however, 9.2% (n = 13) required dose reduction, and 11.42% (n = 16) required an increased dose of desidustat on the follow-up visit. In both Pre-Dialysis and dialysis-dependent patients, there was a sustainable rise in the mean Hb levels at the end of 24 weeks from baseline (1.05 g/dL; p &amp;lt; 0.05) All the patients tolerated desidustat well. In the present study, we didn't observe significant side effects related to the therapy apart from 2.41% (n = 3) cases of Diarrhoea and Vomiting. Conclusion Desidustat is effective in increasing Hb in CKD Anemia patients in the short run. However, Long-term studies are required to establish the efficacy and safety of this novel therapy.

#2815 Single center, single arm, prospective, observational study of desidustat in chronic kidney disease-induced anemia

Abstract Background and Aims Anemia in chronic kidney disease (CKD) is multifactorial. Relative deficiency of erythropoietin is one of the key reasons for decreased RBC production. This anemia is associated with poor quality of life and increases morbidity in CKD patients. Injectable erythropoietin is the standard of care for CKD-anemia, which has safety concerns. Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), stimulates endogenous erythropoiesis and is approved for CKD anemia treatment. Hence, the present study identifies the real-world clinical efficacy and safety of the desidustat treatment for a short duration in CKD anemia. Method This is an open-label, single-center, prospective study. We analyzed the data of 130 patients who are currently in follow-up and received Desidustat as treatment for CKD-anemia. The study is for the duration of 24 weeks. We followed up on patent at 1 month, 3 months, and the end of the study (6 months). Patients were given a 100-mg Desidustat tablet orally three times in a week. The primary outcome is to assess the change in Hb from baseline, and the secondary outcome is the safety of the therapy. Results In this study, we enrolled 130 patients. Of these 130 patients, 58.4% (n = 76) were male and 41.5% (n = 54) were female. The mean age of the study population was 53.6 ± 12.3 years. The majority of the study population was in the pre-dialysis category; 80% (n = 104) and 20% (n = 26) were on dialysis. All the dialysis patients were on three times per week on Dialysis. Diabetes (68%) and hypertension (75%) are the most common co-morbid conditions in patients with CKD anemia. All the patients received desidustat at a 100 mg, three-weekly dose. During each follow-up visit, a significant rise in hemoglobin was observed (p&amp;lt;0.001), as shown in the figure. With desidustat therapy, adverse drug reactions were seen in 5.3% (n = 7) cases: three cases of abdominal pain, two cases of vomiting, and two cases of diarrhea. Conclusion Oral HIF-PHIs and Desidustat showed significant improvement in hemoglobin in CKD anemia patients. More studies require for safety and efficacy in Dialysis dependent CKD - Anemia patients.

#2266 Removal of middle size molecules: effects on the modifications of subgroups of white cell types

Abstract Background and Aims In both classical hemodialysis (HD) and its high convective version, the hemodiafiltration (HDF), the unavoidable contact of blood cells with the filters (e.g. polysulfone), may cause the formation of microaggregates and the release of Inflammatory cytokines. Reducing inflammation and thrombus formation is essential, as these may change the cardiovascular risk of patients undergoing chronic HD. To overcome this problem, removing plasma proteins with greater molecular weight, thereby modifying the protein network around blood cells, might be helpful. Method Synthetic dialyzers (FX 80 CorDiax [Fresenius Medical Care], medium-cutoff filter Theranova 400 [Baxter], Elisio 17-H [Nipro], and BG-U 1.6 [Toray]) have been compared regarding their effects on white blood cell types. We designed a retrospective, dual-center clinical study on patients in ESRD needing substitutive therapy. Groups comparable for age, blood pressure, and body weight have been compared. Changes in albumin, Hb, neutrophils, eosinophils, basophils, monocytes, and platelets have been analysed one month after the treatment. Results The Theranova treatment decreased lymphocytes but was also observed to increase neutrophils and MCV. Platelet count was highest with Elisio-H filters, whereas they were comparable among the other groups. Correlation analysis showed a significant association between platelet counts, neutrophils, and monocytes in all groups. Conversely, the correlation between eosinophils and lymphocytes was significant for all groups except for the Theranova filters. Furthermore, the dialyzers inulin (5.2kDa) clearance was negatively linearly correlated to the lymphocyte counts. Conclusion The recent introduction of MCO filters offers the clinician an adjunctive possibility to modify blood composition in terms of plasma composition and different white blood cells. Further studies may use these unique characteristics in new clinical settings.

#2264 Efficacy and safety of oral iron supplementation with liposomal iron in non-dialysis chronic kidney disease patients with iron deficiency

Abstract Background and Aims Iron deficiency (ID) is very common in patients with non-dialysis dependent chronic kidney disease (NDD-CKD). In these patients, oral iron supplementation is recommended as first-line treatment for ID. However, the efficacy of oral iron supplementation is frequently impaired by a higher incidence of adverse gastrointestinal side effects. Liposomal iron is a compound with ferric pyrophosphate enclosed in a phospholipid nucleus, providing high gastrointestinal absorption and bioavailability and a lower incidence of side effects. However, few data are available on its efficacy in patients with NDD-CKD. Method This single-arm pilot study was carried out in in patients with NDD-CKD stages 1-5 and ID, defined as serum ferritin (SF)&amp;lt;100 ng/mL and/or transferrin saturation (TSAT)&amp;lt; 20%, consecutively seen in two Nephrology units (Naples and Bari) from 01/12/2022 to 01/04/2023. We assessed the efficacy of six months of liposomal iron therapy in correcting ID across three visits after baseline (month 1, 3 and 6). All patients received liposomal iron (30 mg/day twice daily for the first month followed by 30 mg daily for the remaining five months). The primary endpoints were the achievement of SF ≥100 ng/mL and TSAT ≥20%. Secondary outcomes were hemoglobin (Hb) changes and safety of liposomal iron; adherence to the iron supplementation was assessed by monthly pill counting. Changes of continuous variables during the study were analyzed by linear mixed models assuming an unstructured covariance matrix; this was done to take into account the correlation between repeated measures and missing points for patients not completing the study. Change of prevalence of corrected SF and TSAT values from baseline to month 1, 3 and 6 was analyzed by McNemar test. Results 38 patients (65.3 ± 15.2 years, 52.6% males, 35.1% diabetes, eGFR 38.5 ± 28.8 mL/min/1.73 m2) received at least one dose of liposomal iron (safety population). Efficacy population included 34 patients with at least one control visit after baseline. Clinical characteristics of patients enrolled in the two clinics did not differ. In efficacy population, baseline SF was 44 (IQR 19-82) ng/mL and TSAT 14.3 ± 5.9%, corresponding to a percentage of SF&amp;lt;100 ng/mL of 78.9%, and TSAT&amp;lt;20% in 89.5%; 64.7% had both parameters below the cut-offs. Anemia (defined as Hb&amp;lt;12 g/dL in women and &amp;lt;13 g/dL in men) was detected in 22/34 patients. Liposomal iron induced a progressive increase of TSAT from 14.3 ± 5.9%, at baseline to 20.0 ± 7.6% at month-6 (P = 0.009) whereas no difference was detected for SF (Fig. 1A and 1C). Accordingly, at the end of study, the prevalence of TSAT&amp;gt;20% significantly increased from 11.8% to 50.0% (P = 0.002) while correction of SF, mildly improved (from 23.5% to 30.0%, P = 0.214, Fig. 1B and 1D). When patients were stratified by anemia, a significant improvement of TSAT was observed in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, P = 0.012), whereas no significant improvement was found in patients without anemia (P = 0.093). Adherence to iron supplementation was 100% in patients completing the study. Hb values did not significantly increase at month-6 in either anemic (+0.60 ± 1.39 g/dL, P = 0.258) or non-anemic (+0.08 ± 0.78 g/dL, P = 1.0) patients. In safety population (n = 38), 7 patients dropped out (18.4%). In particular, treatment was discontinued in 4 patients in the first month (2 for diarrhea, 1 for dyspepsia and constipation, and 1 for death), 1 patient after 3 months (switch to intravenous iron for symptomatic anemia), and 2 after five months (1 for dyspepsia and 1 for death). Conclusion The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of functional ID (TSAT&amp;lt;20%), with no significant effect on iron storage. The small sample size prevents any causative conclusion, though it may provide some insights into using these compounds in patients with CKD.

#1194 Roxadustat in ESA converted patients with anemia of chronic kidney disease on dialysis: a secondary analysis of ROXSTAR Registry

Abstract Background and Aims Anemia is associated with increased morbidity &amp; mortality in chronic kidney disease (CKD) patients. Around 20% of patients experience erythropoiesis-stimulating agent (ESA) hypo-responsiveness and can't achieve hemoglobin (Hb) treatment target even with a high dose. Higher ESA dose is associated with undesirable outcomes. Roxadustat has demonstrated efficacy and safety in ESA converted CKD anemia patients. We conduct this secondary analysis of ROXSTAR registry (ChiCTR2100046322) to evaluate the Hb response to roxadustat in ESAs converted dialysis-dependent (DD) patients with prior weekly ESA dose ≥10000 U and &amp;lt;10000 U respectively. Method This study used existing data collected in the ROXSTAR Registry. DD patients converted from ESA treatment who received at least one dose of roxadustat, and had at least one post baseline Hb were included. We described the Hb response to roxadustat treatment in patients converted from higher ESA dose (≥10,000 U per week) and from lower ESA dose (&amp;lt;10,000 U per week) at enrollment. The changes from baseline to week 12 &amp; week 24 in Quality of Life (QoL) assessed by SF-36 Vitality &amp; Physical Function subscales, and Rapid Assessment of Physical Activity (RAPA) Strength &amp; Flexibility scores were also analyzed respectively. Results Total 666 ESA converted DD patients were included. For the higher ESA dose group, there were 426 patients (257 male [60.3%]) with a mean (standard deviation [SD]) age of 49.5 [13.1] years, the median (mix, max) dialysis duration was 31.7 (0.2, 307.8) months. For the lower ESA dose group, 240 patients (141 male [58.8%]) with a mean age of 49.7 [13.0] years were enrolled, and median dialysis duration was 36.4 (0.4, 266.1) months. The mean baseline Hb was 98.0 (14.5) g/L in the higher ESA dose group and 102.2 (12.6) g/L in the lower ESA dose group. The median prior weekly ESA dose was 10000 (10000, 50000) U and 6000.0 (300, 9000) U in higher &amp; lower ESA dose groups (Table 1). Mean weekly roxadustat dose during the first 12 weeks (correction phase) was maintained around 300 mg and then decreased to around 260 mg during 12-52 weeks (maintenance phase) for the higher ESA dose group; the dose started from around 300 mg and decreased to 270 mg during the correction phase and then gradually decreased to around 230 mg during the maintenance phase in the lower ESA dose group. The mean Hb change from baseline averaged over weeks 24-36 &amp; 36-52 was 12.1 [95% CI: 10.5, 13.7] g/L &amp; 12.3 [95% CI: 10.7, 13.9] g/L for the higher ESA dose group and 9.9 [95% CI: 8.0, 11.8] g/L &amp; 10.2 [95% CI: 8.3, 12.1] g/L for the lower ESA dose group, respectively. The proportion (%) of patients with mean Hb ≥100 g/L at the same period were 82.3% [95% CI: 78.1%, 86.6%] &amp; 83.6% [95% CI: 79.3%, 87.9%] in the higher ESA dose group and 88.4% [95% CI: 83.6%, 93.1%] &amp; 89.0% [95% CI: 84.3%, 93.7%] in the lower ESA dose group. There was no clinical meaningful change of QoL observed in either group. Conclusion ESA-converted DD patients responded well to roxadustat in terms of anemia correction and Hb maintenance to treatment target, regardless of prior ESA dose. Similar starting doses of roxadustat were used for both groups and then gradually decreased during the maintenance phase (week 12-52) compared to the correction phase (week 1-12) while the magnitude of dose decrease was greater in the lower ESA dose group.

#1168 Responsiveness to roxadustat in chronic kidney disease associated anemia patients by baseline hemoglobin: a secondary analysis of ROXSTAR Registry

Abstract Background and Aims Anemia is a common complication of chronic kidney disease (CKD), and associated with increased morbidity and mortality, as well as a reduced quality of life (QoL). Various studies have shown anemia treatment in CKD patients improved the QoL. However, in ROXSTAR Registry (ChiCTR2100046322), although roxadustat corrected anemia and maintained hemoglobin (Hb) effectively, no improvement in QoL was observed. Hence, we conduct this secondary analysis of ROXSTAR to evaluate the Hb response to roxadustat treatment and the change of QoL in dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients stratified by baseline Hb. Method This was a secondary analysis using existing data collected in the ROXSTAR Registry. DD &amp; NDD Patients who received at least one dose of roxadustat and had at least one post baseline Hb were included. We described the Hb response to roxadustat in patients with lower baseline (Hb &amp;lt;80) g/L &amp; higher baseline Hb (≥80 g/L). The changes from baseline to week 12 &amp; week 24 in Quality of Life (QoL) assessed by SF-36 Vitality (V) &amp; Physical Function (PF) subscales, and Rapid Assessment of Physical Activity (RAPA) Strength &amp; Flexibility scores were also analyzed respectively. Results Overall, 1998 patients (1508 DD patients and 490 NDD patients) were included, there were 238 patients (131 male [55.0%]) with a mean (standard deviation [SD]) age of 49.1 (13.6) years in the lower baseline Hb group, and 1760 patients (947 male [53.8%]) with a mean age of 50.3 (13.5) in the higher baseline Hb group. The overall mean baseline Hb was 97.3 (13.9) g/L, with 71.4 (7.2) g/L and 100.8 (10.5) g/L in the two groups respectively. The median (min, max) ferritin and mean transferrin saturation were 149.6 (3.3, 2304.0) ng/mL &amp; 22.8% (15.5) % in the lower baseline Hb group and 169.8 (3.8, 3966.0) ng/mL &amp; 30.6% (15.7%) in the higher baseline Hb group. More patients with CRP above normal limit were in the lower baseline Hb group (30.7%) compared to patients in the other group (19.7%) (Table 1). Mean weekly roxadustat dose started at 320 mg and was maintained during the first 12 weeks (correction phase) then slightly decreased to 300 mg from week 12 until week 52 (maintenance phase) in patients with baseline Hb &amp;lt;80 g/L, while it was from 286 mg to 260 mg during the correction phase then decreased and maintained at around 230 mg from week 12 to week 52 in patients with baseline Hb ≥80 g/L. The mean Hb change from baseline averaged over weeks 24-36 and 36-52 was 31.9 [95% CI: 29.9, 33.9] g/L &amp; 33.7 [95% CI: 31.8, 35.6] g/L in the lower baseline Hb group, and 11.3 [95% CI: 10.6, 12.0] g/L &amp; 11.1 [95% CI: 10.5, 11.8] g/L in the higher baseline Hb group. The proportion (%) of patients with mean Hb ≥100 g/L averaged over the same period were 58.8% [95% CI: 51.8%, 65.7%] &amp; 68.6% [95% CI: 61.8%, 75.3%] in the lower baseline Hb group, and 86.5% [95% CI: 84.7%, 88.3%] &amp; 88.2% [95% CI: 86.5%, 90.0%] in the higher baseline Hb group. Patients with baseline Hb &amp;lt;80 g/L had numerically higher mean increases from baseline to week 12 and 24 in SF-36 V and PF sub-scores (Table 2), though no clinical meaningful change was observed in either group. Conclusion Roxadustat effectively corrected anemia in DD and NDD patients regardless of baseline Hb level. There was no clinical meaningful improvement in QoL for either group. The weekly dose of roxadustat to correct and maintain Hb was higher in patient with baseline Hb &amp;lt;80 g/L than in patients with baseline Hb ≥80 g/L.

Study of Haemolysis in Patients of Leprosy Being Administered Multi-Drug Therapy at a Tertiary Care Hospital in Western Maharashtra: A Prospective Study.

Dapsone forms the backbone of multi-drug therapy (MDT) in leprosy and many other dermatological disorders. Haemolysis is its common side effect which often necessitates drug stoppage. Currently, wide variation in data of haemolysis with dapsone exists in literature ranging from 24.7% to 83% and none of the studies point towards the timing of onset of haemolysis/timing of maximal haemolysis which is important in therapeutic decision making regarding continuing or stopping the drug. This study aimed to answer such unanswered questions. Primary: To estimate the fall in haemoglobin (Hb) levels after administering MDT for 3 months in patients with leprosy. Secondary: To determine factors associated with Hb change - age, glucose-6-phosphate dehydrogenase (G6PD) status, pole of leprosy and duration of MDT taken (if any). All freshly diagnosed cases of Hansen's disease were studied for 3 months. At baseline, demographic data (age, sex), skin biopsy, slit skin smear and G6PD were taken. Haemoglobin (Hb), serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate transferase (SGPT), serum bilirubin, lactate dehydrogenase (LDH), reticulocyte count, peripheral blood smear (PBS) along with clinical photography was done at baseline, 1, 2 and 3 months. Out of the 48 patients who completed the study: Mean Hb (g/dL) decreased from 13.37 at baseline to a minimum of 12.08 at 2 months, and then increased to 12.34 at 3 months. Of 42 patients (87.5%) with a fall in Hb, 13 (27.1%) had severe (fall >20%), 17 (35.4%) had moderate (fall 10-20%), 12 (25%) had mild fall (fall <10%) and in 6 (12.5%), there was no haemolysis. Reticulocyte count, LDH, SGOT and SGPT were significantly associated with haemolysis. Severe haemolysis occurred more frequently in the lepromatous spectrum. Dapsone causes maximal fall of hemoglobin by 1.29 g/dl at two months following which it increases. The fall of hemoglobin is reversible and hemoglobin starts to increase by 3 months of therapy making cessation of the drug unnecessary in most of the patients.

Synergistic Effect of Naringin and Glimepiride in Streptozotocin-induced Diabetic Rats.

Evaluation of the synergistic effect of Naringin and Glimepiride in streptozotocin (STZ)-induced diabetic rats. Wistar rats were chosen and divided into five groups (n=6). STZ was used for the induction of diabetes. The combination of naringin and glimepiride was administered to diabetic rats. The changes in fasting blood sugar, body weight, Hb, HbA1c, and creatinine were evaluated, and urine was collected and the volume was observed. The lipid profiles like TC, HDL, LDL, and TG were measured. The biochemical parameters SGOT, SGPT, and ALP were analysed. Besides, endogenous antioxidant parameters like SOD, GSH, and catalase were also assessed. Lastly, the histopathological study of the beta cells in islets of the pancreas, glomerulus, and tubules of kidney and liver cells was conducted in all groups. The result shows significant reduction (p<0.001) of blood sugar in the naringin and glimepiride-treated group when compared with the control group (diabetes). Additionally, the combination of Naringin (100 mg/kg) and Glimepiride (0.1 mg/kg) significantly restores the creatinine levels and urine volumes, SGOT, SGPT, and ALP when compared to a single dose of administration. Further, the abnormal lipid profile levels (TC, LDL, TG, and HDL), and endogenous antioxidant enzymes (SOD, GSH, catalase) in diabetic control rats were restored to normal levels in a significant manner. The histopathological result reveals significant alterations, including hypertrophy of islets and mild degeneration, renal necrosis, and inflammation of hepatocytes. A synergistic effect of Naringin and glimepiride was observed during the estimation of various biochemical parameters like body weight, fasting blood sugar, creatinine, urine level, TG, total cholesterol, SGOT, SGPT, ALP, Insulin, HbA1c, antioxidant parameters like SOD, GSH, and catalase in STZ-induced diabetic rats. Further, the combination of therapy improves the protective effect of the pancreas, kidney, and liver, suggesting a potential antidiabetic effect.

Intravenous Iron Supplementation in Pregnancy: A Quality Improvement Project on Maternal Transfusion Reduction [ID 2683469

INTRODUCTION: Intravenous (IV) iron supplementation for patients with iron deficiency anemia in pregnancy has been shown to improve hemoglobin (Hb) levels in the peripartum period and ultimately lead to a decrease in severe maternal morbidity (SMM), specifically blood transfusion. The objective of this study was to analyze the effects of IV iron supplementation on maternal pre-delivery Hb levels after the implementation of an institution-based protocol focused on maternal red blood cell transfusion reduction. METHODS: We performed a retrospective review of patients who received IVFe supplementation after the implementation of a maternal transfusion reduction bundle at our Level IV maternal care center in 2020. We reviewed changes in maternal Hb pre-infusion and pre-delivery over a 3-year period (2020–2023), along with rates of postpartum blood transfusion. Patients were excluded if they received an antepartum blood transfusion. Maternal demographics, ferritin and Hg levels were compared between the two groups using GraphPad Prism software. RESULTS: Two hundred ninety-five patients met inclusion criteria; most patients were Hispanic (71.9%), had Medicaid (51.9%), and underwent a vaginal delivery (76.9%). Mean gestational age at time of infusion was 34.2 weeks (95% CI, 33.7–34.7) The average Hb pre-infusion and pre-delivery were 8.9 (95% CI, 8.8–9.0) and 10.6 (95% CI, 10.4–10.8), respectively. The change in maternal Hb at time of delivery increased by 2 points (P&lt;.0001). Only two patients received a blood transfusion postpartum. CONCLUSION: Implementation of a standardized antenatal IV iron infusion protocol can improve maternal pre-delivery Hb levels and reduce morbidity associated with blood transfusion.

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.