Hypoxia inducible factor (HIF)-stabilizers are being developed for the renal anemia treatment. This small molecules inhibit prolyl hydroxylase domain (PHD)-containing enzymes, causing HIF activation instead of degradation under the state of normoxia, finally increase production of intrinsic erythropoiesis. Current treatment guidelines suggest that renal anemia should be treated mainly with iron and erythropoiesis stimulating agents (ESAs). But there are several complications and concerns such as hypertension, ESA refractory anemia and increased cardiovascular mortality in using ESAs. Advantages of HIF stabilizers over ESAs are orally available, no dose-up requirement for inflammation. So far new HIF stabilizers showed efficacy and safety in renal anemia treatment. This new therapeutic agent may emerge as a standard treatment option for renal anmia treatment.
Anemia ; Anemia, Refractory ; Anoxia ; Erythropoiesis ; Hematinics ; Hepcidins ; Humans ; Hypertension ; Inflammation ; Iron ; Mortality ; Prolyl Hydroxylases ; Renal Insufficiency, Chronic

Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in Korea. We defined anemia when hemoglobin level was lower than 13.0 g/dL in males and 12.0 g/dL in females, or received by erythropoiesis stimulating agents. Overall prevalence of anemia was 45.0% among 2,198 non-dialysis CKD patients from stage 1 to 5. Diabetic nephropathy (DN) as a cause, CKD stages, body mass index (BMI), smoking, leukocyte count, serum albumin, iron markers, calcium, and phosphorus concentration were identified as independent risk factors for anemia. Considering the current coverage of Korean National Health Insurance System, only 7.9% among applicable patients were managed by intravenous iron agents, and 42.7% were managed by erythropoiesis stimulating agents.
Anemia* ; Body Mass Index ; Calcium ; Cohort Studies* ; Diabetic Nephropathies ; Female ; Hematinics ; Humans ; Iron ; Korea ; Leukocyte Count ; Male ; National Health Programs ; Phosphorus ; Prevalence* ; Renal Insufficiency, Chronic* ; Risk Factors ; Serum Albumin ; Smoke ; Smoking

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.
Activins ; Anemia* ; Apoptosis ; Erythrocytes ; Erythropoiesis* ; Erythropoietin ; Hematinics* ; Hemolysis ; Hepcidins ; Humans ; Metabolism ; Miners ; Mortality ; Prolyl-Hydroxylase Inhibitors ; Renal Dialysis ; Renal Insufficiency, Chronic ; Transforming Growth Factors

Blood transfusions were once believed to the most potent and cost-effective method of improving patients' survival outcomes, but accumulating evidence over the past thirty years strongly suggests allogeneic transfusions as independent prognosticators of complications, prolonged hospital stay, and higher costs. A growing body of health care providers in Korea and throughout the world recognize a causal relationship between these adverse outcomes with liberal transfusion policies and call for a universal paradigm shift regarding the management of blood. Currently, the most promising contender is Patient Blood Management (PBM), which has been found to improve patient outcomes by conserving or optimizing the patient's own blood and physiologic reserves and advocating for restrictive transfusion policies. PBM incorporates evidence-based transfusion replacements to address anemia, bleeding, and blood disorders. These various methods–such as intravenous iron, erythropoiesis stimulating agents, coagulating factors, and topical hemostatic agents–are gaining recognition because of their ability to preclude the need for allogenic transfusions while effectively managing the patient's blood.
Anemia ; Blood Transfusion ; Health Personnel ; Hematinics ; Hemorrhage ; Humans ; Iron ; Korea ; Length of Stay ; Methods

Anemia is common in patients with advanced chronic kidney disease (CKD). Though erythropoiesis-stimulating agents (ESAs) have been strongly endorsed in guidelines, it is of particular financial interest. Recently, the reimbursement of ESAs in non-dialytic patients was started by the Korean National Health Insurance System. Thus, we investigated the impact of the reimbursement of ESAs on the anemia care in non-dialytic CKD patients. Medical records of patients with advanced CKD (estimated GFR <30 mL/min/1.73 m2) were reviewed. Use of ESAs, blood transfusion, and hemoglobin concentrations were analyzed from one year prior to reimbursement to three years following. We used multivariable modified Poisson regression to estimate the utilization prevalence ratio (PRs). A total of 1,791 medical records were analyzed. The proportion of patients receiving ESAs increased from 14.8% before reimbursement to a peak 33.6% in 1 yr after reimbursement; thereafter, ESA use decreased to 22.4% in 3 yr after reimbursement (compared with baseline; PR, 2.19 [95% CI, 1.40-3.42]). In patients with Hb <10 g/dL, the proportion of receiving ESAs increased from 32.1% before reimbursement to 66.7% in 3 yr after reimbursement (compared with baseline; PR, 2.04 [95% CI, 1.25-3.32]). Mean hemoglobin concentrations were 10.06±1.54 g/dL before reimbursement and increased to 10.78±1.51 g/dL in 3 yr after the reimbursement change (P=0.001). However, the requirement of blood transfusion was not changed over time. With the reimbursement of ESAs, the advanced CKD patients were more likely to be treated with ESAs, and the hemoglobin concentrations increased.
Adolescent ; Adult ; Aged ; Anemia/complications/*drug therapy/epidemiology ; Blood Transfusion ; Female ; Glomerular Filtration Rate ; Hematinics/*therapeutic use ; Hematocrit ; Hemoglobins/analysis ; Humans ; Male ; Middle Aged ; National Health Programs ; Poisson Distribution ; Prevalence ; Renal Insufficiency, Chronic/complications/*drug therapy/epidemiology ; Republic of Korea/epidemiology ; Retrospective Studies ; Young Adult

A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7-31.5 mIU/mL), carboxyhemoglobin level was 0.6% (range, 0-1.5%), and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.
Aged ; Anemia ; Bone Marrow ; Carboxyhemoglobin ; Erythropoietin ; Hematinics ; Humans ; Kidney Failure, Chronic ; Oxygen ; Polycythemia* ; Renal Dialysis* ; Urinary Bladder Neoplasms

BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. RESULTS: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.
Adult ; Anemia, Iron-Deficiency/blood/diagnosis/*drug therapy/physiopathology ; Biological Markers/metabolism ; Case-Control Studies ; Echocardiography, Doppler ; Female ; Heart Ventricles/*physiopathology/ultrasonography ; Hematinics/*therapeutic use ; Hemoglobins/metabolism ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recovery of Function ; Time Factors ; Treatment Outcome ; *Ventricular Function, Left ; *Ventricular Pressure ; *Ventricular Remodeling ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of iron protein succinylate (IPS) oral solution in preventing and treating anemia of prematurity (AOP).

METHODSSixty premature infants less than 35 weeks of gestation were randomly divided into IPS (n=30) and polysaccharide iron complex (PIC) groups(n=30). Treatment began at two weeks after birth. The infants received IPS or PIC in addition to recombinant human erythropoietin. On days 14, 28, 42, and 60 after treatment, hemoglobin (Hb), red blood cell count(RBC), hematocrit (HCT), percentage of reticulocytes, serum iron, and serum ferritin were determined. Liver and renal functions were evaluated before and after treatment.

RESULTSThere were significant differences in the changing trends of RBC and HCT between the two groups (P<0.05). In the IPS group, RBC and HCT gradually decreased after birth, but began to rise gradually on days 28 and 42 of treatment; in the PIC group, RBC and HCT kept decreasing from birth to day 60 of treatment. On day 60 of treatment, the IPS group had significantly higher levels of Hb, RBC, HCT, serum iron, and serum ferritin than the PIC group (P<0.05). No notable adverse events occurred in either group.

CONCLUSIONSIPS oral solution has good efficacy and tolerability in preventing and treating AOP.

Administration, Oral ; Anemia, Neonatal ; blood ; drug therapy ; prevention & control ; Erythrocyte Count ; Female ; Hematinics ; therapeutic use ; Hematocrit ; Humans ; Infant, Premature ; Iron ; metabolism ; Male ; Metalloproteins ; adverse effects ; therapeutic use ; Solutions ; Succinates ; adverse effects ; therapeutic use

Anemia and malnutrition are common complications of end-stage renal disease. They increase the morbidity and mortality of end-stage renal disease patients and affect their quality of life. However, the mechanisms of anemia and malnutrition are already known, and their therapeutic guidelines are being established. Appropriate iron supplementation and the development of erythropoiesis-stimulating agents have made anemia easier to manage than in the past. In addition, adequate protein and calorie intake have allowed end-stage renal disease patients to maintain a neutral or positive nitrogen balance. These therapeutic approaches have decreased the morbidity and mortality of these end-stage renal disease patients. This review is a summary of the treatment of anemia and nutrition in end-stage renal disease, based on the Kidney Disease Outcomes Quality Initiative (KDOQI) guideline on anemia and other anemia guidelines, and also on the KDOQI guideline on nutrition and European Best Practice Guideline (EBPG) on nutrition.
Anemia ; Hematinics ; Humans ; Iron ; Kidney Diseases ; Kidney Failure, Chronic ; Malnutrition ; Nitrogen ; Practice Guidelines as Topic ; Protein-Energy Malnutrition ; Quality of Life

Previous studies reported the beneficial effect of erythropoietin (EPO) in acute injuries. We followed patients with and without acute kidney injury (AKI) after coronary artery bypass grafting (CABG) and evaluated the effect of EPO on long-term outcome. We also assessed the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. Seventy-one patients scheduled for elective CABG were randomly given either 300 U/kg of EPO or saline before CABG. The primary outcome was AKI, and the secondary outcome was the all-cause-mortality and composite of all-cause-mortality and end stage renal disease (ESRD). Twenty-one patients had AKI, 14 (66.7%) in the placebo group and 7 (33.3%) in the EPO group (P = 0.05). Also, uNGAL was higher in the patients with AKI than in those without AKI at baseline, 2, 4, 24, and 72 hr after CABG (P = 0.011). Among patients with AKI, 2-week creatinine (Cr) was not different from baseline Cr in the EPO group, but 2-week Cr was significantly higher than baseline Cr in the placebo group (P = 0.009). All-cause-mortality (P = 0.022) and the composite of all-cause-mortality and ESRD (P = 0.003) were reduced by EPO. EPO reduces all-cause-mortality and ESRD in patients with AKI, largely due to the beneficial effect of EPO on recovery after AKI.
Acute Kidney Injury/etiology/mortality/*prevention & control ; Acute-Phase Proteins/urine ; Aged ; Aged, 80 and over ; Biological Markers/urine ; Coronary Artery Bypass/*adverse effects ; Creatinine/analysis ; Double-Blind Method ; Erythropoietin/*therapeutic use ; Female ; Hematinics/*therapeutic use ; Humans ; Kaplan-Meier Estimate ; Lipocalins/urine ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Proto-Oncogene Proteins/urine ; ROC Curve ; Recombinant Proteins/therapeutic use ; Risk Factors ; Treatment Outcome