scholarly journals Effects of Oral Intake of Olive Leaf Extract on Hematological Parameters: A Double-Blinded, Randomized, Placebo-Controlled Trial in Progress

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 927-927
Author(s):  
Farhana Ferdousi ◽  
Masud Alam ◽  
Risa Araki ◽  
Sofya Suidasari ◽  
Miki Yokozawa ◽  
...  
Keyword(s):  
Hematological Parameters ◽  
Oral Intake ◽  
Erythroid Differentiation ◽  
Deficiency Anemia ◽  
Olive Leaf ◽  
Review Committee ◽  
Double Blinded ◽  
Hb Concentration ◽  
Post Hoc ◽  
Rbc Count

Abstract Background: Anemia is one of the major public health problems that affected 2.36 billion individuals worldwide in 2015. Half of all causes of anemia are iron or other nutrient deficiency anemia (WHO, 2015). Currently available treatment options for anemia include iron or other nutrient supplementation, nutritional interventions in the form of food fortification, blood transfusion, and erythropoietic agent infusion. However, conventional treatments are not without adverse effects. In this context, medicinal plants with bioactive components have been receiving considerable attention from researchers as natural hematinic agents complemented with or alternatives to conventional treatment. Olive leaf (Olea europaea L. Oleaceae) extract (OLE) is rich in bioactive compounds and have been reported to have several health benefits (Gorzynik-Debicka et al., 2018). Previously we showed that apigetrin and apigenin, components of OLE, induced erythroid differentiation in K562 cells (Tsolmon et al., 2011 and Isoda et al., 2014). Also, OLE and its phenolic compounds induced erythroid differentiation in hHSCs (Kondo et al., 2021, Samet et al., 2015). Additionally, we have reported that long-term consumption of OLE tea increased RBC count, Hb%, and hematocrit (Ht) in female volunteers aged between 40 - 70 years old (Ferdousi et al., 2019). However, none of the participants were anemic at the baseline. Therefore, in the present study, we aimed to investigate the effects of oral intake of OLE on hematological parameters in healthy to mildly anemic young adults. Study Design and Methods A double-blinded, randomized, placebo-controlled study will be conducted in Bangladesh. Total 165 apparently healthy adults with Hb level at least 10g/dl for females (nonpregnant, non-breastfeeding) and 11g/dl for males, and aged between 18 to 59 years will be enrolled from the local community. Major exclusion criteria will include currently pregnant women or breastfeeding mothers, moderate to severe anemia (Hb concentration < 10 g / dL for women and < 11 g / dL for men), any medical condition, such as hematological diseases, malignant tumors, aplastic anemia, uncontrolled hypertension, chronic kidney disease, irritable bowel syndrome, and cardiovascular diseases, and currently taking medicine for diabetes or hypertension and taking regular iron or other supplements, etc. After providing informed written consent, study participants will be randomly assigned to placebo, 250 mg OLE and 500 mg OLE groups. Participants will take OLE or placebo capsules in two divided doses every day for 12 weeks. Hematological parameters, Hb concentration, RBC count, WBC count, Ht, MCV, MCH, MCHC, serum Fe and ferritin levels will be investigated at baseline and after 6 and 12 weeks of intervention. Liver and renal function tests will be conducted for safety assessment. Additionally, lipid profile will be investigated to understand how lipid parameters will be regulated if anemia condition is improved by OLE intervention (Araki et al., 2019). Given that fatigue is one of the most common symptoms of anemia, we will also evaluate the effect of OLE on the score of each item of the Fatigue Assessment Scale (FAS) questionnaire during the intervention. The analysis will be carried out on an intention-to-treat basis involving all the participants who will consume the test samples at least once. We will replace the missing data from dropouts using the baseline observation carried forward method. ANOVA with Bonferroni's post hoc test will be used for normally distributed data; otherwise, the Mann-Whitney U test or Kruskal-Wallis H(K) test will be used. Categorical variables will be compared by the Chi-square or Fisher's exact test. A one-way repeated-measures ANOVA with Bonferroni's post hoc test (Within-group) and ANOVA followed by Bonferroni's post hoc test (between-group) will be performed. Significance is at p < 0.05. This protocol is registered with UMIN-CTR Clinical Trial (UMIN000039023), and has been approved by University of Tsukuba Hospital Clinical Research Ethics Review Committee (R01-292) and the Ethical Review Committee of icddr,b (PR-21017). This study is funded by the Japan Society for the Promotion of Science (19K20106) and partly by the Japan Science and Technology Agency-SATREPS (JPMJSA1506). Disclosures Suidasari: Nutrition Act Co. Ltd.: Current Employment. Yokozawa: Nutrition Act Co. Ltd.: Current Employment. Yamauchi: Nutrition Act Co. Ltd.: Current Employment.

scholarly journals Application of innovative hemocytometric parameters and algorithms for improvement of microcytic anemia discrimination

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Margreet Schoorl ◽  
Marianne Schoorl ◽  
Johannes Van Pelt ◽  
Piet C.M. Bartels
Keyword(s):  
Iron Deficiency ◽  
Blood Cell ◽  
Iron Deficiency Anemia ◽  
Red Blood Cell ◽  
Hematological Parameters ◽  
Deficiency Anemia ◽  
Zinc Protoporphyrin ◽  
Distribution Width ◽  
New Algorithms ◽  
Rbc Count

Hemocytometric parameters like red blood cell (RBC) count, mean red blood cell volume (MCV), reticulocyte count, red blood cell distribution width (RDW-SD) and zinc protoporphyrin (ZPP) are frequently established for discrimination between iron-deficiency anemia and thalassemia in subjects with microcytic erythropoiesis. However, no single marker or combination of tests is optimal for discrimination between iron-deficiency anemia and thalassemia. This is the reason why many algorithms have been introduced. However, application of conventional algorithms, only resulted in appropriate classification of 30-40% of subjects. In this mini-review the efficacy of innovative hematological parameters for detection of alterations in RBCs has been considered. It refers to parameters concerning hemoglobinization of RBCs and reticulocytes and the percentages microcytic and hypochromic RBCs, for discrimination between subjects with iron-deficiency anemia (IDA) or thalassemia as well as a combination of both. A new discriminating tool including the above mentioned parameters was developed, based on two precondition steps and discriminating algorithms. The percentage microcytic RBCs is considered in the first pre-condition step. MCV, RDW-SD and RBC count are applied in the second precondition step. Subsequently, new algorithms, including conventional as well as innovative hematological parameters, were assessed for subgroups with microcytic erythropoiesis. The new algorithms for IDA discrimination yielded results for sensitivity of 79%, specificity of 97%, positive and negative predictive values of 74% and 98% respectively. The algorithms for beta-thalassemia discrimination revealed similar results (74%, 98%, 75% and 99% respectively). We advocate that innovative algorithms, including parameters reflecting hemoglobinization of RBCs and reticulocytes, are integrated in an easily accessible software program linked to the hematology equipment to improve the discrimination between IDA and thalassemia.

scholarly journals THERAPEUTIC EFFECTS OF HYDRO-ETHANOLIC EXTRACT OF Nigella sativa (BLACK SEED) ON SOME HAEMATOLOGICAL PARAMETERS OF ALBINO RATS AFTER LEAD EXPOSURE

2020 ◽  
Vol 14 (2) ◽  
pp. 131-135
Author(s):  
Abubakar A ◽  
◽  
Tukur MA ◽  
Ibrahim BM ◽  
Isa BI ◽  
...  
Keyword(s):  
Lead Poisoning ◽  
Nigella Sativa ◽  
Hematological Parameters ◽  
Seed Extract ◽  
Albino Rats ◽  
Therapeutic Effects ◽  
Hb Concentration ◽  
Nigella Sativa Seed ◽  
Haematological Indices ◽  
Rbc Count

Background: Lead poisoning is a great public health concern in Africa and Nigeria, especially regions where illegal mining activities occurs such as widespread gold ore mining in Zamfara by artisan miners using rudimentary and unsafe processing techniques. Lead (Pb) which often have no biological function remain in the system causes havoc and distortion of normal physiologic functions. Currently, the toxic effects of lead poisoning are clinically treated using chelation therapy which have been associated with many side effects and setbacks. Since ancient times, medicinal plants have been used as a major source of treatment for numerous human diseases. Plants that possess hematinic and antioxidant properties in the plant kingdom are often used in such scenarios. One of such plants is Nigella sativa commonly known as black cumin. Objectives: In this study, therapeutic effects of hydro-ethanolic extracts of Nigella sativa was assessed on hematological parameters of lead- poisoned albino rats as a curative therapy for management of lead poisoning. Method: Thirty- five (35) adult albino wistar rats of both sexes were used for this study. Group I (Normal control) received 2ml/kg of distilled water, Group II (Negative control), Group III treated with 10 mg/kg of Meso-2,3 Dimercaptosuccinic acid (DMSA), IV treated with 200 mg/kg of Nigella sativa seed extract, V treated with 400 mg/kg of Nigella sativa seed extract, and VI treated with 800mg/kg of Nigella sativa seed extract for Group VII (Recovery) were allowed to recover without treatment. The study lasted for a duration of 21days. Blood samples were collected from the rats through cardiac puncture after anesthetizing the animals and analysed for haematological parameters which included RBC count, PCV, Hb concentration, platelet count, WBC profile and haematological indices using an automated digital blood analyser. Results: Nigella sativa seed extract significantly (P<0.05) reversed the adverse effect of Lead exposure on RBC count, PCV, Hb concentration, platelet count, WBC profile and haematological indices. Conclusion: Nigella sativa showed therapeutic effects on hematological parameters and indices of lead poisoned albino rats.

scholarly journals Haemato-biochemical profile during different stages of lactation in local Sahiwal crossbred dairy cows at Savar area of Dhaka district of Bangladesh

2021 ◽  
Vol 7 (1) ◽  
pp. 1-5
Author(s):  
Sajibul Hasan ◽  
Mohammad Alam Miah ◽  
Md Kamrul Islam
Keyword(s):  
Dairy Cows ◽  
Early Stage ◽  
Hematological Parameters ◽  
Total Leucocyte Count ◽  
Biochemical Profile ◽  
Stage Of Lactation ◽  
Normal Limits ◽  
Mean Corpuscular Haemoglobin ◽  
Hb Concentration ◽  
Rbc Count

The present study was carried out to investigate the haemato-biochemical profile during different stages of lactation in local Sahiwal crossbreed dairy cows at Savar area of Dhaka district of Bangladesh. Twenty four local Sahiwal crossbreed cows were selected randomly from different small farms and divided into three groups: early stage lactation (1-3 months), mid stage lactation (4-6 months) and late stage lactation (7-9 months). Blood samples were collected during three stages of lactation. There were no statistical significant (p<0.05) variations observed in hematological parameters amongst the three stage of lactation. Although the packed cell volume (PCV), hemoglobin (Hb) concentration and RBC count were found lowest in early stage of lactation than the other groups. Total leucocyte count (TLC), platelet count (PLT), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were recorded within normal limits. Similarly, biochemical parameters were observed statistically non-significant amongst the groups studied. The glucose level was recorded lowest in early stage of lactation; whereas, the protein and creatinine concentrations were slightly higher in this stage. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) were not varied amongst the three groups of cows. Data generated during the current study may be useful as reference values for the scientific community. Asian J. Med. Biol. Res. March 2021, 7(1): 1-5

scholarly journals Influence of iron deficiency anemia on glycated hemoglobin levels in non-diabetic Saudi women

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199015
Author(s):  
Iman Abdullah Bindayel
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Hba1c Level ◽  
Glycated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Hemoglobin Concentration ◽  
Deficiency Anemia ◽  
Saudi Women ◽  
Hb Concentration ◽  
Rbc Count

Objective Studies of patients with iron deficiency anemia (IDA) have shown a relationship between high glycated hemoglobin (HbA1c) and low hemoglobin (Hb) concentration. The present study was conducted to determine the influence of IDA on HbA1c in non-diabetic women. Methods Fifty-nine Saudi women (20 to 50 years old) were enrolled and categorized into groups according to their circulating hemoglobin concentration: Non-IDA (Hb ≥7.45 mmol/L; n = 38) and IDA (Hb ≤7.44 mmol/L; n = 21). The IDA group was further subdivided according to the severity of the IDA, as follows: mild (Hb 6.83 to 7.44 mmol/L; n = 9) and moderate–severe (Hb <6.83 mol/L; n = 12). HbA1c, Hb, ferritin, fasting blood glucose, and red blood cell (RBC) count were measured in each participant. Results HbA1c did not significantly differ between the groups, but the absolute HbA1c level was significantly lower in the mild and moderate–severe anemia groups than the non-anemic group, and was positively associated with Hb, ferritin, and RBC count. In addition, the HbA1c level was inversely associated with the Hb concentration. Conclusions HbA1c is significantly associated with parameters related to IDA in non-diabetic Saudi women. Therefore, assessment of IDA-related parameters is recommended prior to making a diagnosis of diabetes.

scholarly journals Iron-Containing Contraceptives and Their Effect on Hemoglobin and Biomarkers of Iron Status: A Narrative Review

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2340
Author(s):  
Jordie A. J. Fischer ◽  
Carolina S. Sasai ◽  
Crystal D. Karakochuk
Keyword(s):  
Oral Contraceptive ◽  
Iron Deficiency ◽  
Contraceptive Use ◽  
Iron Status ◽  
Cost Effective ◽  
Narrative Review ◽  
Deficiency Anemia ◽  
Oral Contraceptive Use ◽  
Contraception Use ◽  
Hb Concentration

Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. The aims of this narrative review are: (i) to describe the relationship between oral contraceptive use and both anemia and iron status in women; (ii) to describe the current formulations of iron-containing oral contraceptives (ICOC) available on the market; and (iii) to systematically review the existing literature on the effect of ICOC on biomarkers of anemia and iron status in women. We discovered 21 brands of ICOC, most commonly including 25 mg elemental iron as ferrous fumarate, for seven days, per monthly tablet package. Our search identified one randomized trial evaluating the effectiveness of ICOC use compared to two non-ICOC on increasing hemoglobin (Hb) and iron status biomarker concentrations in women; whereafter 12 months of contraception use, there were no significant differences in Hb concentration nor markers of iron status between the groups. ICOC has the potential to be a cost-effective solution to address both family planning needs and iron deficiency anemia. Yet, more rigorous trials evaluating the effectiveness of ICOC on improving markers of anemia and iron deficiency, as well as investigating the safety of its consumption among iron-replete populations, are warranted.

scholarly journals HEMATOLOGICAL PARAMETERS AND BODY COMPOSITION OF SOCCER PLAYERS

2018 ◽  
Vol 24 (3) ◽  
pp. 202-205 ◽  
Author(s):  
Allana Kelly Bussollaro ◽  
Barbara Nara de Freitas ◽  
Raíssa Maria Fadel ◽  
Gabriela Siqueira Lara ◽  
Priscila Dabaghi Barbosa ◽  
...  
Keyword(s):  
Body Composition ◽  
Serum Iron ◽  
Binding Capacity ◽  
Hematological Parameters ◽  
Soccer Players ◽  
Mean Corpuscular Hemoglobin ◽  
Corpuscular Hemoglobin ◽  
Level Of Evidence ◽  
Hematological Changes ◽  
Post Hoc

ABSTRACT Introduction: Soccer players may experience hematological changes that could be detrimental to their health status. In addition, inadequate body composition may impair performance. Objective: To assess body composition and hematological changes over a year in soccer players. Methods: A retrospective observational study was conducted. Age, weight, height, body composition, blood count, serum iron, serum ferritin, serum transferrin and total iron binding capacity data were collected from the athletes’ medical records in the months of January, May and August of 2015 and January of 2016. Body mass index was also calculated. For the statistical analyses, the Anova and post-hoc Tukey’s post-hoc tests were used for the quantitative variables and the Chi-square test for the qualitative variables. The significance level adopted was p<0.05. Results: Data were evaluated for 51 athletes with a mean age of 23.53 ± 3.11 years, 77.10 ± 6.56 kg, 1.80 ± 0.07 and 15.6 ± 2.89% body fat (BF). We observed significant (p<0.05) changes in mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, cell size and eosinophils during the period evaluated. Among the athletes, 21.6% had decreased hematocrit levels and 3.9% had hemoglobin levels below the reference range. A BF% greater than 16% was significantly related to serum iron depletion (p = 0.01). Conclusion: Small significant hematological changes during the competitive year were observed, but without significant changes in body composition. Level of Evidence III; Study of nonconsecutive patients; without consistently applied reference ‘‘gold’’ standard.

scholarly journals Application of Bayesian Decision Tree in Hematology Research: Differential Diagnosis of β-Thalassemia Trait from Iron Deficiency Anemia

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Mina Jahangiri ◽  
Fakher Rahim ◽  
Najmaldin Saki ◽  
Amal Saki Malehi
Keyword(s):  
Differential Diagnosis ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Hematological Parameters ◽  
False Positive Rate ◽  
Deficiency Anemia ◽  
Beta Thalassemia ◽  
Bayesian Tree ◽  
Thalassemia Trait ◽  
Cart Algorithm

Objective. Several discriminating techniques have been proposed to discriminate between β-thalassemia trait (βTT) and iron deficiency anemia (IDA). These discrimination techniques are essential clinically, but they are challenging and typically difficult. This study is the first application of the Bayesian tree-based method for differential diagnosis of βTT from IDA. Method. This cross-sectional study included 907 patients with ages over 18 years old and a mean (±SD) age of 25 ± 16.1 with either βTT or IDA. Hematological parameters were measured using a Sysmex KX-21 automated hematology analyzer. Bayesian Logit Treed (BLTREED) and Classification and Regression Trees (CART) were implemented to discriminate βTT from IDA based on the hematological parameters. Results. This study proposes an automatic detection model of beta-thalassemia carriers based on a Bayesian tree-based method. The BLTREED model and CART showed that mean corpuscular volume (MCV) was the main predictor in diagnostic discrimination. According to the test dataset, CART indicated higher sensitivity and negative predictive value than BLTREED for differential diagnosis of βTT from IDA. However, the CART algorithm had a high false-positive rate. Overall, the BLTREED model showed better performance concerning the area under the curve (AUC). Conclusions. The BLTREED model showed excellent diagnostic accuracy for differentiating βTT from IDA. In addition, understanding tree-based methods are easy and do not need statistical experience. Thus, it can help physicians in making the right clinical decision. So, the proposed model could support medical decisions in the differential diagnosis of βTT from IDA to avoid much more expensive, time-consuming laboratory tests, especially in countries with limited recourses or poor health services.

scholarly journals Effect of vitamin C supplementation on hematological parameters in smokeless tobacco chewers

2021 ◽  
Vol 12 (3) ◽  
pp. 2088-2094
Author(s):  
Jaywant S. Thorat ◽  
Anand G. Joshi ◽  
Kanchan C. Wingkar
Keyword(s):  
Platelet Count ◽  
Vitamin C ◽  
Smokeless Tobacco ◽  
Hematological Parameters ◽  
Protective Effects ◽  
Baseline Study ◽  
Vitamin C Supplementation ◽  
Baseline Values ◽  
Wbc Count ◽  
Rbc Count

The present study was aimed to evaluate the effect of Vitamin C (VC) supplementation on hematological parameters in Smokeless Tobacco (ST) chewers.  A total of 338 subjects aged between 31 to 60 years (168 ST chewers and 170 ST non-chewers) participated in the present study. ST chewers were further divided into 3 subgroups with respect to ST chewing duration in years. Subjects of both the groups were examined at the baseline study and after 45 days of supplementation of 1 g of Vitamin C (VC) for hematological parameters.  WBC count (p=0.04), granulocytes % (p=0.0007), HCT (p=0.01) and MCV (p=0.04) were significantly increased whereas, monocytes % (p=0.002) and platelet count (p<0.0001) were significantly decreased in ST chewers as compared to controls. After supplementation of VC, WBC count (p<0.001) and granulocytes % (p<0.0001) were significantly decreased and lymphocytes % (p=0.008), monocytes % (p<0.0001), RBC count (p=0.01) and Hb content (p=0.006) were significantly increased in ST chewers as compared to their baseline values. In conclusion,  the use of ST had deleterious effects on hematological parameters; however, supplementation of 1 g of VC showed protective effects on hematological parameters.

scholarly journals Maternal Hepcidin Suppression Is Essential for Healthy Pregnancy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Veena Sangkhae ◽  
Tomas Ganz ◽  
Elizabeta Nemeth
Keyword(s):  
Iron Deficiency ◽  
Molecular Mechanisms ◽  
Hematological Parameters ◽  
Critical Role ◽  
Physiological Mechanism ◽  
Deficiency Anemia ◽  
Private Company ◽  
Iron Stores ◽  
Primary Mouse

Iron is essential for maternal and fetal health during pregnancy, and iron requirements increase substantially in the second half of gestation1. However, the molecular mechanisms ensuring increased iron availability during pregnancy are not well understood. Hepcidin is the key iron-regulatory hormone and functions by occluding and degrading the iron exporter ferroportin (FPN) to inhibit dietary iron absorption and mobilization of iron from stores. In healthy human and rodent pregnancies, maternal hepcidin decreases starting in the second trimester and is nearly undetectable by late pregnancy2,3 (Figure A). We explored the role of maternal and embryo hepcidin in regulating embryo iron endowment using mouse models. By generating combinations of dams and embryos lacking hepcidin or not, we showed that in normal mouse pregnancy, only maternal but not embryo or placental hepcidin determines embryo iron endowment4. Maternal hepcidin was inversely related to embryo iron stores, and embryos from hepcidin-deficient dams had significantly higher hepatic iron stores regardless of their own hepcidin genotype. When maternal hepcidin was elevated during the second half of pregnancy in mice by administering a hepcidin mimetic, this led to dose-dependent embryo iron deficiency, anemia, and in severe cases, embryo death4. Embryos were particularly sensitive to maternal iron restriction as they developed iron deficiency in the liver and the brain even when maternal hematological parameters were unaffected. These data highlight the critical role of maternal hepcidin suppression for heathy pregnancy. Yet, the physiological mechanism of maternal hepcidin suppression remains unknown. We showed in mice that maternal hepcidin decreases prior to a significant decrease in liver iron and without any changes in serum iron, suggesting that maternal hepcidin suppression is not driven solely by iron deficiency. Using an in vitro model, we determined that the placenta secretes a hepcidin-suppressing factor. Exposure of primary mouse hepatocytes to supernatants from cultured human placenta cells, but not control media, suppressed hepcidin mRNA more than 10-fold (Figure B) and for up to 48hrs. The suppressive factor in the supernatant was &gt;100kDa in size and not associated with exosomes. Studies to identify the placenta-derived hepcidin suppressor are ongoing. In summary, suppression of maternal hepcidin is essential to ensure adequate iron supply for transfer to the fetus and for the increase in maternal red blood cell mass2, and a placenta-derived hepcidin suppressor likely plays an important role in this adaptation. 1Fisher AL and Nemeth E, Am J Clin Nutr, 2017 2Sangkhae V et al, JCI, 2020 3van Santen S et al, Clin Chem Lab Med, 2013 4Sangkhae V et al, Blood, 2020 Figure 1 Disclosures Ganz: Global Blood Therapeutics: Consultancy; Ionis Pharmaceuticals: Consultancy; American Regent: Consultancy; Rockwell: Consultancy; Vifor: Consultancy; Astellas: Consultancy; Akebia: Consultancy; Gossamer Bio: Consultancy; Silarus Therapeutics: Current equity holder in private company; Sierra Oncology: Consultancy; Ambys: Consultancy; Disc Medicine: Consultancy; Intrinsic LifeSciences: Current equity holder in private company. Nemeth:Intrinsic LifeSciences: Current equity holder in private company; Silarus Therapeutics: Current equity holder in private company; Ionis Pharmaceuticals: Consultancy; Protagonist: Consultancy; Vifor: Consultancy.

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