losartan-potassium and Diabetes-Mellitus

Erythropoietin (EPO) is the main regulator of red blood cell production. Since the 1990s, EPO has been used for the treatment of anemia associated with end-stage renal failure and chemotherapy. The erythropoietin receptors were found on other organs such as the brain, spinal cord, heart and skin. In addition, it has been shown that many tissues produce and locally release EPO in response to hypoxic, biochemical and physical stress. In cellular, animal and clinical studies, EPO protects tissues from ischemia and reperfusion injury, has antiapoptotic effects and improves regeneration after injury. In this article, we mainly review the nonhematopoietic effects and new possible clinical indications for EPO.

Topics: Animals; Cardiovascular Diseases; Cognition; Diabetes Mellitus; Erythropoietin; Humans; Kidney; Memory; Neovascularization, Physiologic; Neurodegenerative Diseases; Neuroprotective Agents; Obesity; Retina

Diabetes mellitus impacts almost 200 million individuals worldwide and leads to debilitating complications. New avenues of drug discovery must target the underlying cellular processes of oxidative stress, apoptosis, autophagy, and inflammation that can mediate multi-system pathology during diabetes mellitus.. The authors examine the novel directions for drug discovery that involve: the β-nicotinamide adenine dinucleotide (NAD(+)) precursor nicotinamide, the cytokine erythropoietin, the NAD(+)-dependent protein histone deacetylase SIRT1, the serine/threonine-protein kinase mammalian target of rapamycin (mTOR), and the wingless pathway. Furthermore, the authors present the implications for the targeting of these pathways that oversee gluconeogenic genes, insulin signaling and resistance, fatty acid beta-oxidation, inflammation, and cellular survival.. Nicotinamide, erythropoietin, and the downstream pathways of SIRT1, mTOR, forkhead transcription factors, and wingless signaling offer exciting prospects for novel directions of drug discovery for the treatment of metabolic disorders. Future investigations must dissect the complex relationship and fine modulation of these pathways for the successful translation of robust reparative and regenerative strategies against diabetes mellitus and the complications of this disorder.

Topics: Animals; Diabetes Mellitus; Drug Delivery Systems; Drug Discovery; Erythropoietin; Humans; Hypoglycemic Agents; Niacinamide; Signal Transduction; TOR Serine-Threonine Kinases

Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycemia and vascular complications, leading to significant morbidity and mortality. All forms of diabetes are ultimately related to insufficient functional pancreatic β-cell mass to maintain euglycemia. In this context, the promotion of β-cell survival and function is a fundamental issue of direct relevance to diabetes prevention and treatment. Although first identified as a hematopoietic factor that promotes erythropoiesis and erythrocyte survival, an accumulating body of evidence suggests that erythropoietin (EPO) may also exert cytoprotective effects on non-erythroid tissues, including the brain, kidney, blood vessels, and pancreatic β cells. Recent reports have demonstrated the biological effects of EPO on the pancreatic β cells and its potential preventative and therapeutic role in diabetes. This review will focus on the emerging extra-hematopoietic roles of EPO and its potential protective role in diabetes.

Topics: Animals; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Energy Metabolism; Erythropoietin; Hematopoietic System; Humans; Models, Biological

Erythropoiesis-stimulating agents (ESA) are used to treat renal anemia. The TREAT study (Trial to Reduce Cardiovascular Events with Aranesp Ther- apy) of diabetic patients with chronic kidney disease (CKD) found that the risk of stroke was significantly higher than in the control arm. This raises the question as to what causes this phenomenon. Platelets may play a crucial role in this context. Atherogenesis involves complex interactions between platelets and monocytes (platelet-monocyte crosstalk) and with endothelial cells. Platelets are activated in cases of diabetes mellitus, especially. During atherogenesis, partial functions of platelets other than those inhibited by aspirin, as a cyclooxygenase inhibitor, or by adenosine diphosphate receptor P2Y(12)antagonists, such as thienopyridines, are of relevance. During platelet-monocyte crosstalk, specifically, an important role is played by adhesion receptors such as selectins and integrins. In addition, ESA cause platelet activation by direct and indirect mechanisms. Antagonistic thereto is a renal bleeding tendency in cases of severe CKD, due to platelet dysfunction, which can be remedied with appropriate renal replacement therapy and administration of ESA in order to reach a hemoglobin (Hb) level of 10 g/dl. However, if the Hb level exceeds 10 g/dl, the even stronger platelet activation caused by ESA, combined with the activation caused by diabetes, leads to a prothrombotic state, which in patients with severe atherosclerosis can result in acute atherothrombotic complications, in the genesis of which platelets play a key role. This would be one hypothesis for explaining the increased incidence of strokes in the TREAT study.

Topics: Anemia; Atherosclerosis; Blood Platelets; Darbepoetin alfa; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Erythropoietin; Female; Hematinics; Hemoglobinometry; Humans; Integrins; Intracranial Embolism; Male; Monocytes; Platelet Activation; Randomized Controlled Trials as Topic; Receptor Cross-Talk; Renal Replacement Therapy; Selectins

Anemia is one of the world's most common preventable conditions, yet it is often overlooked, especially in people with diabetes mellitus. Diabetes-related chronic hyperglycemia can lead to a hypoxic environment in the renal interstitium, which results in impaired production of erythropoietin by the peritubular fibroblasts and subsequent anemia. Anemia in patients with diabetes mellitus might contribute to the pathogenesis and progression of cardiovascular disease and aggravate diabetic nephropathy and retinopathy. Anemia occurs earlier in patients with diabetic renal disease than in nondiabetic individuals with chronic kidney disease. Although erythropoietin has been used to treat renal anemia for nearly two decades, debate persists over the optimal target hemoglobin level. Most guidelines recommend that hemoglobin levels be maintained between 105g/l and 125g/l. The suggested role of anemia correction--to prevent the progression of left ventricular hypertrophy in patients with diabetes mellitus--is yet to be established. However, an emphasis on regular screening for anemia, alongside that for other diabetes-related complications, might help to delay the progression of vascular complications in these patients.

Topics: Anemia; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Hemoglobins; Humans; Models, Biological

Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO), and members of the mammalian forkhead transcription factors of the O class (FoxOs), may offer the greatest promise for new treatment regimens, since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. Yet, EPO and FoxOs may sometimes have unexpected and undesirable effects that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as the complex role that EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

Topics: Animals; Biomarkers; Cell Survival; Diabetes Mellitus; Erythropoietin; Forkhead Transcription Factors; Humans; Neoplasms; Oxidative Stress; Receptors, Erythropoietin

Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.

Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Darbepoetin alfa; Diabetes Mellitus; Erythropoietin; Humans; Insulin; Protein Deficiency; Proteins; Recombinant Proteins

Global use of erythropoietin (EPO) continues to increase as a proven agent for the treatment of anemia. Yet, EPO is no longer believed to have exclusive biological activity in the hematopoietic system and is now considered applicable for a variety of disorders such as diabetes, Alzheimer's disease, and cardiovascular disease. Treatment with EPO is considered to be robust and can prevent metabolic compromise, neuronal and vascular degeneration, and inflammatory cell activation. On the converse side, observations that EPO administration is not without risk have fueled controversy. Here we present recent advances that have elucidated a number of novel cellular pathways governed by EPO to open new therapeutic avenues for this agent and avert its potential deleterious effects.

Topics: Animals; Apoptosis; Diabetes Mellitus; Erythropoietin; Gene Expression Regulation; Hematopoiesis; Humans; Inflammation; Models, Biological; Neovascularization, Pathologic; Neurodegenerative Diseases; Oxidative Stress; Signal Transduction

Diabetes mellitus (DM) is a significant healthcare concern worldwide that affects more than 165 million individuals leading to cardiovascular disease, nephropathy, retinopathy, and widespread disease of both the peripheral and central nervous systems. The incidence of undiagnosed diabetes, impaired glucose tolerance, and impaired fasting glucose levels raises future concerns in regards to the financial and patient care resources that will be necessary to care for patients with DM. Interestingly, disease of the nervous system can become one of the most debilitating complications and affect sensitive cognitive regions of the brain, such as the hippocampus that modulates memory function, resulting in significant functional impairment and dementia. Oxidative stress forms the foundation for the induction of multiple cellular pathways that can ultimately lead to both the onset and subsequent complications of DM. In particular, novel pathways that involve metabotropic receptor signaling, protein-tyrosine phosphatases, Wnt proteins, Akt, GSK-3beta, and forkhead transcription factors may be responsible for the onset and progression of complications form DM. Further knowledge acquired in understanding the complexity of DM and its ability to impair cellular systems throughout the body will foster new strategies for the treatment of DM and its complications.

Topics: Alzheimer Disease; Animals; Apoptosis; Blood Glucose; Diabetes Mellitus; Erythropoietin; Glycogen Synthase Kinases; GTP-Binding Proteins; Humans; Insulin Resistance; Mitochondria; Models, Biological; Oxidative Stress; Phosphatidylinositol 3-Kinases; Wnt Proteins

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in people with diabetes and in those with chronic kidney disease (CKD). Diabetes, occurring in epidemic proportions in the United States and worldwide, is also the leading cause of CKD and kidney failure. Identification of modifiable risk factors for CVD in patients with diabetes and CKD is thus of paramount importance. Anemia is increasingly recognized as a potential CVD risk factor in patients with diabetic nephropathy, in whom it is generally more severe and occurs at an earlier stage of CKD. In this review, we discuss the epidemiologic evidence, pathophysiologic mechanisms, and the current research findings, highlighting the role of anemia as a potential modifiable risk factor for CVD in patients with diabetic nephropathy, a particularly vulnerable population for CVD.

Topics: Anemia; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Humans; Risk Factors

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hematinics; Humans; Kidney Failure, Chronic; Recombinant Proteins; Treatment Outcome

Anaemia is an important component of diabetic nephropathy but only recently has it attracted the attention of diabetologists and nephrologists. In diabetic patients, anaemia is the result of diminished erythropoietin production and, to a lesser degree, of increased excretion of erythropoietin in the urine, whereas erythropoietin responsiveness remains unchanged. Although erythropoietin concentrations are predictive of the rate of progression of renal disease, epidemiological studies have failed to show lower haemoglobin concentrations in patients with diabetic compared with non-diabetic renal disease with impaired renal function. However, inappropriately low erythropoietin concentrations and anaemia have been reported in subcohorts of diabetic patients. Further studies are required to determine whether reversal of anaemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, retinopathy and peripheral arterial disease.

Topics: Anemia; Chronic Disease; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Humans; Kidney Diseases; Kidney Failure, Chronic; Prevalence

To investigate the impact of alpha-lipoic acid (ALA) on inflammation, oxidative stress, anemia, and glycemic parameters and their association with cardiovascular risk in diabetic patients on hemodialysis.. In this multi-center, randomized, controlled study, 60 diabetic patients on hemodialysis were randomized into control group (n=30) which received Epoetin-alpha plus insulin therapy, and alpha-lipoic acid group (n=30) which received the same treatment plus alpha-lipoic acid (ALA) 600 mg once daily. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), creatinine, urea, blood urea nitrogen (BUN), hemoglobin (Hb), iron parameters, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and fructosamine were measured at baseline and six months after intervention. The ankle-brachial index (ABI) was used to evaluate the clinical outcome. Erythropoietin resistance index (ERI), the weekly cost of Epoetin-alpha doses, and the total cost were calculated.. The two groups were statistically similar at baseline. After the intervention, as compared to the control group, ALA group showed significant reductions in serum levels of hs-CRP, TNF-α, 8-OHdG (p<0.001), urea, and BUN (p=0.029) with significant elevations in Hb concentration (p<0.001), serum iron (p=0.037) and transferrin saturation (p<0.001). ALA group showed a significant decline in FBG (p=0.004), HbA1c (p<0.001), fructosamine (p=0.005), ERI (p<0.001), weekly doses, and the weekly cost of Epoetin-alpha, and the total cost (p<0.001). ALA provided a cardio-protective effect, whereas the percentage of patients with acceptable ABI (0.9-1) was significantly higher in ALA group than in the control group (p=0.024), and those with abnormally low ABI (<0.9) were lower in the ALA group.. Due to its efficacy and safety, alpha-lipoic acid represents a pharmaco-economic supplement for diabetic patients on hemodialysis. Further trials are needed for complete evaluation of ALA effects.

Topics: Anemia; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus; Erythropoietin; Fructosamine; Glycated Hemoglobin; Glycemic Control; Heart Disease Risk Factors; Humans; Iron; Prospective Studies; Renal Dialysis; Risk Factors; Thioctic Acid; Tumor Necrosis Factor-alpha; Urea

The diabetic foot ulcer (DFU) is a major disabling complication of diabetes mellitus. Growing evidence suggests that topical erythropoietin (EPO) can promote wound healing. The aim of this study is to clinically assess the efficacy of a proprietary topical EPO-containing hydrogel for treating DFUs. We conducted a randomized, controlled trial in 20 patients with DFUs. After a 14-day screening period, the DFUs of 20 eligible participants who fulfilled the inclusion criteria were randomly assigned (1:1) to either a 12-week of daily treatment with topical EPO and standard-of-care (SOC) or SOC treatment alone. The DFUs were assessed weekly until week 12. The primary outcome was 75% ulcer closure or higher. After 12 weeks of treatment, 75% ulcer closure was achieved in 6 of the 10 patients whose DFUs were treated with topical EPO and in one of the 8 patients whose DFUs were treated with SOC alone. The mean area of the DFUs that were treated with topical EPO and SOC was significantly smaller than those treated with SOC alone (1.2 ± 1.4 cm

Topics: Diabetes Mellitus; Diabetic Foot; Erythropoietin; Humans; Prospective Studies; Single-Blind Method; Treatment Outcome; Wound Healing

Im Rahmen der vorliegenden Studie sollte der Einfluss des Weichteilschadens auf das klinische Ergebnis nach offener Ellenbogenluxation untersucht werden.. Von Oktober 2008 bis August 2015 wurden insgesamt 230 Patienten mit Ellenbogenluxation behandelt. Diese retrospektive Studie umfasst 21 Fälle von offenen Ellenbogenluxationen. Das Durchschnittsalter der Patienten betrug 49 Jahre alt (20–83 Jahre), 6 Patienten waren weiblich (29%), 15 männlich (71%). Das Bewegungsausmaß des verletzten und unverletzten Ellenbogens wurde erhoben und das funktionelle Ergebnis u. a. mittels Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS) und dem Disability of Arm, Shoulder and Hand (DASH) Score erfasst. Zusätzlich wurden Komplikationen und Revisionsoperationen aufgezeichnet. Der Einfluss des Weichteilschadens (I°/II° offen vs. III° offen) und des Luxationstyps (einfach vs. komplex) auf das klinische Ergebnis wurde analysiert.. Offene Ellenbogenluxationen können mit einem zufriedenstellenden klinischen Ergebnis einhergehen. Insbesondere komplexe offene Ellenbogenluxationen sind jedoch sehr komplikationsbehaftet, wobei neurovaskuläre Komplikationen am häufigsten auftreten.. The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.. The results indicated differential patterns of Inhibition of Return between the High and Low shape/weight based self-worth groups. The High group displayed increased inhibition of return for the shape/weight stimuli relative to control stimuli, while the Low group displayed reduced inhibition of return for the shape/weight stimuli compared to control stimuli. The ED group displayed a similar pattern of results to the High group, but this did not reach significance.. The current findings indicate that young women without an eating disorder who base their self-worth on shape/weight display a pattern of avoidance of shape/weight stimuli that is in direct contrast to those at low risk of developing eating disorders. The possible implications of these specific patterns of inhibition of return across those at varying levels of risk for an eating disorder are discussed along with their implications for intervention approaches.. These results indicated that Sr. An unusually high HbA

Topics: Activities of Daily Living; Acute Disease; Adalimumab; Adaptation, Physiological; Adenosine Triphosphate; Adipose Tissue; Administration, Intravaginal; Adolescent; Adsorption; Adult; Adverse Childhood Experiences; Age Distribution; Age Factors; Aged; Aged, 80 and over; Air Pollution, Indoor; Aldehyde Oxidase; Alginates; Alloys; alpha-Globins; Aluminum Hydroxide; Alveolar Bone Loss; Anaerobiosis; Anesthesia, General; Anesthetics; Animals; Anovulation; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Apoptosis; Bacillus cereus; Bacterial Typing Techniques; Bacteroidetes; Base Composition; Biocompatible Materials; Biofilms; Biological Availability; Biological Transport; Biosensing Techniques; Bipolar Disorder; Blood Glucose; Body Mass Index; Bone Regeneration; Boranes; Brachial Artery; Butyric Acid; Candida albicans; Carbon; Carcinoembryonic Antigen; Cell Differentiation; Cell Line, Tumor; Cell Respiration; Cell Survival; Cells, Cultured; Cerebrovascular Circulation; Charcoal; Child; Child Health; China; Chloride Channels; Chlorides; CHO Cells; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromium; Chronic Disease; Chronic Periodontitis; Circular Dichroism; Cities; Cohort Studies; Comamonadaceae; Comorbidity; Coronary Artery Disease; Corrosion; Cricetinae; Cricetulus; Cross Infection; Cross-Sectional Studies; Crowding; Culture Media; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Diarylheptanoids; Diclofenac; Disability Evaluation; Diterpene Alkaloids; DNA; DNA Mutational Analysis; DNA, Bacterial; Drug Liberation; Drug Resistance, Multiple, Bacterial; Electrochemical Techniques; Electrodes; Electrolytes; Endothelium, Vascular; Enterococcus faecalis; Epithelial Cell Adhesion Molecule; Epithelial Cells; Erbium; Erythropoietin; Ethanol; Ethylenediamines; Fast Foods; Fatty Acids; Female; Fermentation; Ferric Compounds; Fibroblasts; Flavobacteriaceae; Fluorides; Fluorodeoxyglucose F18; Food Microbiology; Formaldehyde; Furaldehyde; Gamma Cameras; Gene Expression; Geologic Sediments; Glucose Tolerance Test; Glycated Hemoglobin; Glycolipids; Glycosylation; Gracilaria; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guanine; Health Surveys; HeLa Cells; Hemoglobins, Abnormal; Hexosamines; High Fructose Corn Syrup; High-Intensity Interval Training; Hip Fractures; Hippocampus; HLA-B27 Antigen; Hospitalization; Housing; Humans; Hydrogen-Ion Concentration; Hydrolysis; Hydroxides; Hypercapnia; Hypertension; Hypocreales; Hypromellose Derivatives; Image Processing, Computer-Assisted; Incidence; Indole Alkaloids; Indonesia; Inflammation Mediators; Infrared Rays; Insulin Resistance; Intercalating Agents; Ion Transport; Ionophores; Japan; Kinetics; Kluyveromyces; Letrozole; Linear Models; Lipopolysaccharides; Liposomes; Liver; Lung Diseases; Magnesium Hydroxide; Magnetic Resonance Spectroscopy; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Middle Aged; Mitochondria; Mitochondria, Muscle; Molecular Docking Simulation; Molecular Structure; Muscle, Skeletal; Mutant Proteins; Mutation; Mutation, Missense; Nanocomposites; Nanoparticles; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Nucleic Acid Hybridization; Obesity; Occupational Exposure; Oceans and Seas; Odds Ratio; Organometallic Compounds; Osteogenesis; Ovulation Induction; Oxidation-Reduction; Particle Size; Periodontal Ligament; Permeability; Phaseolus; Phenotype; Philippines; Phosphatidylethanolamines; Phospholipids; Photochemical Processes; Phylogeny; Pichia; Pigmentation; Plant Extracts; Polycystic Ovary Syndrome; Polysaccharides; Postprandial Period; Pregnancy; Pregnancy Rate; Prevalence; Product Surveillance, Postmarketing; Progesterone; Progestins; Protein Engineering; Pseudomonas aeruginosa; Psoriasis; Public Facilities; Rats; Rats, Wistar; Receptors, Thyrotropin; Recombinant Proteins; Reproducibility of Results; Republic of Korea; Retrospective Studies; Rhodobacteraceae; Risk; Risk Assessment; Risk Factors; RNA, Ribosomal, 16S; ROC Curve; Saccharomyces cerevisiae; Salinity; Saliva; Seawater; Seaweed; Sensitivity and Specificity; Sequence Analysis, DNA; Sex Factors; Silver Compounds; Smokers; Social Class; Socioeconomic Factors; Soil Microbiology; Solubility; Soy Foods; Spectrometry, Mass, Electrospray Ionization; Spondylitis, Ankylosing; Staphylococcus aureus; Static Electricity; Steroids; Strontium; Sucrose; Surface Properties; Survival Rate; Sweden; Swine; Synapses; Synchrotrons; Tandem Mass Spectrometry; Tannins; Tea; Temperature; Terpenes; Thalidomide; Thermodynamics; Thiadiazoles; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Time Factors; Tissue Distribution; Titanium; Toilet Facilities; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ubiquinone; Urinary Tract Infections; Vaginal Creams, Foams, and Jellies; Venezuela; Vitamin K 2; Waist Circumference; Waste Disposal, Fluid; Wastewater; Water Microbiology; Water Pollutants, Chemical; Whole Body Imaging; X-Ray Diffraction; Young Adult; Ytterbium; Yttrium; Yttrium Radioisotopes; Zinc Compounds

Methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor activator (CERA), is reported to be effective in managing renal anemia but there is little data about CERA in Japan. This study aimed to ascertain the effects of CERA in Japanese hemodialysis patients and the appropriate starting dose of CERA when switching from other erythropoiesis-stimulating agents. We switched 61 stable hemodialysis patients to 4-weekly intravenous CERA, from either epoetin beta (rHuEPO) or darbepoetin alpha (DA). When determining the initial dose of CERA, we used guidelines recommended by the Japanese supplier for switching from rHuEPO, but for DA we based the CERA dose on European reports, because no Japanese guidelines exist. Fifty-two patients completed the 28-week study. Hemoglobin was maintained within the target range (10.0-12.0 g/dL). The required CERA dose decreased over the 28 weeks. The hemoglobin level and CERA dose stabilized faster when switching from DA. CERA showed similar efficacy in diabetic and non-diabetic patients. The effect of CERA is similar regardless of whether patients switch from low- or high-dose erythropoiesis-stimulating agents. In conclusion, CERA is effective for Japanese hemodialysis patients at a lower dose than expected.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Diabetes Mellitus; Dose-Response Relationship, Drug; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Japan; Male; Middle Aged; Polyethylene Glycols; Practice Guidelines as Topic; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Comorbidity; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Retrospective Studies; Survival Analysis; Treatment Outcome

The objective of our study was to assess the influence of residual renal function and other factors on epoetin requirements in chronic peritoneal dialysis patients. Fifty-one stable patients (mean age +/- SD: 52 +/- 13 years; 20 women) without recent bleeding, bone marrow disease or malignancy were recruited in four Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal equilibration test results and relevant clinical and laboratory parameters were recorded. The epoetin resistance index was expressed as a weekly epoetin dose/body weight/hemoglobin concentration. Twenty-four percent of the patients did not need epoetin treatment, the rest were treated with epoetin-beta in a dose of 70 +/- 56 U/kg per week s.c.; the hemoglobin concentration was 124 +/- 15 g/L. Ferritin >100 microg/L and transferrin saturation >20% fulfilled 63% of patients whose epoetin resistance index was not significantly lower (0.43 +/- 0.5 U/kg per week per g/L vs 0.6 +/- 0.72 U/kg per week per g/L, P = 0.502). No difference was found between diabetic and non-diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, was associated with increased epoetin resistance index (0.56 +/- 0.59 vs 0.3 +/- 0.4 U/kg per week per g/L, P = 0.038). No correlation between epoetin resistance index and residual glomerular filtration rate was found (r = -0.2, P = 0.173). A multiple linear regression analysis showed C-reactive protein, intact parathormone level, female sex and treatment with angiotensin system antagonists to be the independent predictors influencing epoetin resistance index. Our results show that systemic inflammation, secondary hyperparathyroidism and angiotensin system antagonist treatment are the most important modifiable parameters affecting epoetin requirements in stable peritoneal dialysis patients.

Topics: Adolescent; Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Kidney; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins; Sex Factors; Slovenia; Transferrin

Urea can dissociate in vivo to form isocyanic acid which can react with hemoglobin to form carbamylated hemoglobin. Previous work has shown that formation of carbamylated hemoglobin depends upon both the severity and the duration of renal failure. To determine whether carbamylated hemoglobin can be used as an assessment of the adequacy of hemodialysis treatment, we prospectively studied 55 stable patients who regularly attended our hospital dialysis program. Carbamylated hemoglobin was greater in those patients with a Kt/V of < or = 1.1 compared to those with a Kt/V of > 1.1 (120 +/- 8 micrograms VH/gHb versus 99 +/- 7, P < 0.01), and there was a negative correlation with Kt/V (r = -0.37, P = 0.007). There were positive correlations between carbamylated hemoglobin and the time-averaged urea concentration (r = 0.4, P = 0.004), and a negative correlation with the urea reduction ratio (r = -0.37, P = 0.01). Carbamylated hemoglobin may therefore be a useful marker of the degree of uremia, just as glycosylated hemoglobin is used in the assessment of patients with diabetes mellitus.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Carbamates; Diabetes Mellitus; Erythropoietin; Female; Hemoglobin A; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Sex Factors; Uremia

Topics: Acute Kidney Injury; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Humans; Kidney; Nephrology

Topics: Aged; Anemia, Iron-Deficiency; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus; Erythropoiesis; Erythropoietin; Female; Hematinics; Hepcidins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Transferrin; Renal Dialysis; Transferrin

Erythropoietin (EPO), which is clinically used for renal anaemia, reportedly exerts beneficial pleiotropic effects in atherosclerosis. This aim of this study was to investigate the effects of EPO on macrophage inflammation and polarization under hyperglycaemic conditions and to identify the effects of EPO-treated macrophage supernatants (SNs) on endothelial cell (EC) function.. Peritoneal macrophages (pMΦs) were isolated from normal, diabetic or EPO-injected mice. Pro-inflammatory factors were detected by qRT-PCR and ELISA, and macrophage phenotype markers were evaluated by flow cytometry. High glucose culture was used to mimic the hyperglycaemic microenvironment of diabetes mellitus (DM) in vitro. After exposure to various doses of stimuli, macrophage inflammation and phenotype were detected via ELISA, qRT-PCR and flow cytometry. The underlying mechanism was investigated through western blotting. To examine the communication between macrophages and ECs, ECs were cultured with the SN of macrophages treated with different stimuli, and the tube formation ability of ECs was detected using Matrigel. The VEGF, ICAM-1 and VCAM-1 protein expression levels were determined by western blotting, and the nitric oxide (NO) and endothelin-1 (ET-1) expression levels were measured with a nitric oxide indicator and by ELISA, respectively.. EPO treatment increased the M2 macrophage population and decreased the number of M1 macrophages. EPO decreased the secretion of pro-inflammatory factors, including TNF-α, iNOS and IL-6. The JAK2/STAT3 signalling pathway was also identified as being involved in the M1 macrophage transition. The SN of macrophages treated with EPO (SN-EPO) presented increased NO and ET-1 levels and decreased ICAM-1 and VCAM-1 levels. Tube formation assays revealed that the SN-EPO promoted the ability of ECs to form capillary-like structures in vitro. In contrast, AZD1480, a JAK2 inhibitor, abolished this SN-EPO effect.. EPO treatment alleviated the inflammatory reaction in DM mice and inhibited M1 polarization through the JAK2/STAT3 pathway. Moreover, EPO treatment promoted the tube formation ability of ECs in a VEGF-dependent manner and decreased the production of adhesion molecules, a vasodilator and a vasoconstrictor.

Topics: Animals; Cell Polarity; Diabetes Mellitus; Erythropoietin; Humans; Hyperglycemia; Inflammation; Intercellular Adhesion Molecule-1; Janus Kinase 2; Macrophages; Macrophages, Peritoneal; Male; Mice, Inbred C57BL; Neovascularization, Physiologic; Phenotype; Signal Transduction; STAT3 Transcription Factor; Vascular Cell Adhesion Molecule-1

Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.R.A.) is a drug for the treatment of renal anemia. In this study, we investigated the effect of C.E.R.A. on vascular endothelial function as evaluated by flow-mediated dilation (FMD) and the relationship between hematopoiesis and FMD in diabetic nephropathy rats.. Male Spontaneously Diabetic Torii rats (SDT, 22 weeks old) were used. C.E.R.A. (0.6, 1.2 μg/kg) was administered subcutaneously once every 2 weeks for 8 weeks. At 1 week after last administration (31 weeks old), we assessed FMD in the femoral arteries of anesthetized rats using a high-resolution ultrasound system. FMD was also measured 1 week after single C.E.R.A. treatment (5.0 μg/kg) to examine the influence of hematopoiesis.. Flow-mediated dilation was significantly decreased in SDT rats before the start of C.E.R.A. treatment (22 weeks old). Repeated administration of C.E.R.A. dose-dependently improved FMD in SDT rats (31 weeks old) without changing blood glucose, nitroglycerin-induced vasodilation, or kidney function. Long-term administration of C.E.R.A. improved the state of endothelial nitric oxide synthase uncoupling in the femoral arteries of SDT rats, which showed a positive correlation with FMD. On the other hand, there was no correlation between FMD and Hb or Hct in SDT rats. Furthermore, at 1 week after single administration of C.E.R.A., FMD was not significantly improved although hemoglobin levels were comparable with levels following long-term C.E.R.A.. Long-term treatment with C.E.R.A. improved FMD in SDT rats even after onset of endothelial dysfunction.

Topics: Animals; Biomarkers; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Erythropoietin; Femoral Artery; Hematopoiesis; Hemoglobins; Male; Nitric Oxide Synthase Type III; Polyethylene Glycols; Rats, Inbred Strains; Recovery of Function; Signal Transduction; Time Factors; Vasodilation

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.

Topics: Diabetes Mellitus; Electronic Health Records; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Humans; Hypertension; Kidney Failure, Chronic; Male; Models, Biological; Practice Guidelines as Topic; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; United States

Inflammation contributes to hemopoiesis by lowering responses to epoetin (EPO) and to an increase in the mortality of patients on hemodialysis. However, nutritional status might alter associations among inflammation, EPO responsiveness, and the risk of mortality. We assessed the effect of inflammation on mortality according to nutritional status among EPO responses in a cohort of prevalent hemodialysis patients.. The observational cohort study analyzed data from the Japanese Dialysis Registry (2005-2006; n = 36,956; mean follow-up 11.5 months). Patients were categorized into tertiles of the EPO responsiveness index (ERI; the weekly weight-adjusted EPO dose [IU/kg/week] divided by hemoglobin [g/dL]) and an EPO-free group. Body mass index (BMI) and C-reactive protein (CRP) levels were measured.. Bimodal peaks indicated associations between CRP and BMI in each group. Hazard ratio (HR) curves of CRP for mortality according to BMI in the upper ERI tertile, particularly among those with diabetes mellitus (DM), were reverse J-shaped. However, HR curves in the other groups were increased below a threshold BMI of 21 kg/m(2). These associations were confirmed in propensity score-matched populations.. Risk of CRP for death is apparently changed by BMI in hemodialysis patients with a lower EPO response, especially in those with DM.

Topics: Aged; Body Mass Index; C-Reactive Protein; Cohort Studies; Diabetes Mellitus; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Inflammation; Male; Middle Aged; Nutritional Status; Renal Dialysis; Renal Insufficiency

We purposed to determine the impact of erythropoietin on altering glucose metabolism in the settings of in vitro and in vivo experiments. The acute effect of erythropoietin on lowering blood glucose levels was studied in animal experiments. In [³H]-deoxy-D-glucose isotope studies we measured glucose uptake with insulin and erythropoietin using 3T3-L1 cells cultured under normal or high glucose conditions. Altered activation of Akt and ERK pathways was evaluated in immunoblot analyses. Immunocytochemistry was conducted to determine the glucose transporter 4 translocation to the plasma membrane. Addition of erythropoietin significantly lowered blood glucose levels in vivo in rats. The glucose uptake was markedly increased by erythropoietin treatment (at concentrations 0.15, 0.3, and 0.625 ng/ml) in adipocytes grown in high glucose medium (p<0.05), but it remained unaltered in cells under normal glucose conditions. Significant increase of phosphorylation of ERK and Akt was detected due to erythropoietin (p<0.05). Co-administration of erythropoietin and insulin resulted in higher phosphorylation of Akt and [³H]-deoxy-D-glucose uptake in adipocytes than insulin treatment alone. We found that erythropoietin induced the trafficking of glucose transporter 4 to the plasma membrane. Our data showed that erythropoietin significantly decreased blood glucose levels both in vivo and in vitro, in part, by increasing glucose uptake via the activation of Akt pathway. Preliminary data revealed that adipocytes most likely exhibit a specific receptor for erythropoietin.

Topics: 3T3 Cells; Animals; Biological Transport; Diabetes Mellitus; Down-Regulation; Erythropoietin; Glucose; Glucose Transporter Type 4; Humans; Male; Mice; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley

New perspectives have emerged regarding the processes associated with depressive disorders and their many comorbid conditions. Particular attention has been paid to the potential role of inflammatory factors in promoting these illnesses. These inflammatory responses include those elicited by pathogenic stimuli, as well as sterile inflammatory processes, such as those related to severe or chronic stress. These diverse challenges may activate common processes in which cytokines, which are inflammatory signaling molecules, provoke the dysregulation of several growth factors, including brain-derived neurotrophic factor, fibroblast growth factor-2, macrophage migration inhibitory factor, and erythropoietin. The result of such dysregulation favors the development of depressive disorders and their comorbid illnesses, such as heart disease, diabetes, autoimmune conditions, and poststroke depression.

Topics: Animals; Brain-Derived Neurotrophic Factor; Comorbidity; Cytokines; Depressive Disorder; Diabetes Mellitus; Erythropoietin; Fibroblast Growth Factor 2; Heart Diseases; Humans; Inflammation Mediators; Interleukin-6; Macrophage Migration-Inhibitory Factors; Models, Biological; Models, Psychological; Signal Transduction; Stress, Psychological; Tumor Necrosis Factor-alpha

To evaluate the renal production of erythropoietin (EPO) in relation to filtration function in patients with diabetic kidney lesion.. The investigation enrolled 183 patients with types 1 and 2 diabetes mellitus (DM), of whom 128 were diagnosed as having diabetic kidney lesion. Serum EPO levels were measured by enzyme immunoassay. Patients who had a glomerular filtration rate (GFR) of below 15 ml/min/1.73 m2 and received erythropoiesis-stimulating agents were excluded from the investigation.. The mean serum EPO levels in the patients with diabetic kidney lesion did not vary with the presence or absence of anemia, the degree of albuminuria, or GFR. A physiological inverse relationship was found between the level of EPO and that of hemoglobin in the blood of the patients with DM without kidney disease and in those with renal lesion and GFR > or = 60 ml/min/1.73 m2. The magnitude of the association of the values increased as GFR was higher. The level of EPO was found to be unassociated with hemoglobin in patients with GFR < 60 ml/min/1.73 m2.. In the patients with diabetic kidney lesion, serum EPO concentrations did not depend on the stage of chronic kidney disease and the degree of albuminuria in spite of more severe anemia as renal failure progressed. These patients showed inadequate EPO production just in early diminished renal filtration function.

Topics: Adult; Albuminuria; Anemia; Diabetes Complications; Diabetes Mellitus; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged

The use of higher erythropoietin (EPO) doses is associated with an increased risk of an adverse outcome and increased mortality in patients with renal failure. Resistin is related to heart disease, and may contribute to an increased atherosclerotic risk. We hypothesized that a link between resistin and EPO responsiveness may exist. We therefore investigated the relationship between resistin and the EPO resistance index (ERI) in nondiabetic hemodialysis (HD) patients. Fifty-seven patients enrolled in the study underwent HD for ≥ 3 months and intravenous EPO therapy to maintain a target hemoglobin (Hb) level of 11.0 g/dl. The ERI was defined as the weekly EPO dose per unit Hb per body weight. The mean patient age was 52.6 ± 11.9 years and the mean time on dialysis was 4.9 ± 4.4 years. Serum Hb and ERI were 10.4 ± 0.7 g/dl, and 13.3 ± 7.0 (IU/kg/week/g/dl), respectively. Serum resistin levels were 23.6 ± 9.3 µg/L. EPO resistance is associated with low body mass index (BMI) (coefficient β =-0.393, p = 0.002) and with high serum resistin levels (coefficient β = 0.332, p = 0.018). According to a multiple regression analysis, the serum resistin level was a significant independent factor related to EPO resistance (p = 0.017). The results suggest that serum resistin levels reflect EPO responsiveness in nondiabetic HD patients. Resistin may therefore be considered as a new marker of EPO responsiveness in HD patients.

Topics: Biomarkers; Diabetes Mellitus; Drug Resistance; Erythropoietin; Female; Humans; Linear Models; Male; Middle Aged; Renal Dialysis; Resistin

It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD).. We hypothesized that ESRD patients with relative thrombocytosis (platelet count >300 × 10(3)/μL) have a higher mortality rate and that this association may be related to malnutrition-inflammation cachexia syndrome (MICS).. We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001-2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis.. The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 ± 78 × 10(3)/μL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 × 10(3)/μL (reference), the all-cause (and cardiovascular) mortality rate with platelet counts between 300 and <350, between 350 and <400, and ≥400 ×10(3)/μL were 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P < 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them.. Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies.

Topics: Adult; Aged; Albumins; Atherosclerosis; Black or African American; Cachexia; Cause of Death; Cohort Studies; Creatinine; Diabetes Mellitus; Dialysis; Dietary Proteins; Erythropoietin; Female; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Malnutrition; Middle Aged; Platelet Count; Prevalence; Thrombocytosis

Anemia is common in chronic kidney disease (CKD). The CHOIR study found increased risk of a composite cardiovascular outcome when anemia was treated with epoetin-alfa to a target hemoglobin level of 13.5 as compared with 11.3 g/dl. Whether this increase applies to all patient subgroups equally is unclear. We discuss an analysis by Szczech and colleagues of the effects of the higher hemoglobin target in CKD patients with diabetes mellitus or congestive heart failure.

Topics: Anemia; Chronic Disease; Diabetes Mellitus; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Kidney Diseases; Recombinant Proteins

Diabetes mellitus (DM) impacts a significant portion of the world's population and care for this disorder places an economic burden on the gross domestic product for any particular country. Furthermore, both Type 1 and Type 2 DM are becoming increasingly prevalent and there is increased incidence of impaired glucose tolerance in the young. The complications of DM are protean and can involve multiple systems throughout the body that are susceptible to the detrimental effects of oxidative stress and apoptotic cell injury. For these reasons, innovative strategies are necessary for the implementation of new treatments for DM that are generated through the further understanding of cellular pathways that govern the pathological consequences of DM. In particular, both the precursor for the coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)), nicotinamide, and the growth factor erythropoietin offer novel platforms for drug discovery that involve cellular metabolic homeostasis and inflammatory cell control. Interestingly, these agents and their tightly associated pathways that consist of cell cycle regulation, protein kinase B, forkhead transcription factors, and Wnt signaling also function in a broader sense as biomarkers for disease onset and progression.

Topics: Animals; Cell Cycle; Cell Survival; Diabetes Mellitus; Erythropoietin; Forkhead Transcription Factors; Humans; Niacinamide; Oxidative Stress; Proto-Oncogene Proteins c-akt; Signal Transduction; Wnt Proteins

Anaemia occurs in 25% of people attending hospital diabetes clinics, but this may not be representative of all people with diabetes. We aimed to determine the prevalence of anaemia in a prospective population-based sample stratified by estimated glomerular filtration rate (eGFR) using the 4-point Modification of Diet in Renal Disease (MDRD) formula.. All 7331 patients on our district register were stratified by eGFR. Seven hundred and thirty were approached by letter on two occasions. Two hundred and thirty-four (32%) returned questionnaires and blood samples. Responders (R), non-responders (NR) and the whole cohort (C) were similar: mean +/- sd age R 61.7 +/- 12.7 years; NR 61.3 +/- 15.1 years; C 61.8 +/- 14.2 years; diabetes duration R 8.8 +/- 8.6 years; NR 8.2 +/- 7.9 years; C 7.5 +/- 7.8 years, Type 1 diabetes R 10.1%, NR 10.8%, C 9.4%. Anaemia was defined using World Health Organization criteria: haemoglobin < 13 g/dl for men, < 12 g/dl for women.. Previously undiagnosed anaemia was present in 15% of the whole group, 36% with eGFR < 60 ml/min per 1.73 m(2) and 9% of those with eGFR > 60 ml/min per 1.73 m(2). Anaemia was as a result of erythropoietin deficiency in 34%, abnormal haematinics in 40% and was unexplained in 26% of patients. Five per cent of the patients had anaemia below the treatment threshold of 11 g/dl.. The prevalence of unrecognized anaemia in population-based cohorts is lower than that in hospital-based studies. Current clinical surveillance in the UK is failing to detect anaemia in stage 3-5 chronic kidney disease (eGFR < 60 ml/min per 1.73 m(2)) and current guidelines will not detect 9% of diabetic patients with anaemia and an eGFR > 60 ml/min per 1.73 m(2).

Topics: Aged; Anemia; Diabetes Mellitus; Diabetic Nephropathies; England; Erythropoietin; Female; Glomerular Filtration Rate; Hematinics; Humans; Male; Middle Aged; Population Groups; Prevalence; Prospective Studies; Surveys and Questionnaires

Darbepoetin alpha is effective for renal anemia when epoetin is insufficient. We previously reported that the dose conversion ratio from epoetin alpha to darbepoetin alpha was 1:350.5 after 24 weeks of follow-up. This study assessed the conversion ratio in stable Japanese hemodialysis patients after 52 weeks.. A total of 104 hemodialysis patients who were stable on intravenous epoetin alpha were switched to intravenous darbepoetin alpha according to the 1:200 rule. Then they were followed for 52 weeks to assess changes of hemoglobin and the darbepoetin alpha dose.. Eighty-five patients completed the study. Their hemoglobin increased very rapidly during the first 8 weeks. The final conversion ratio was 1:286.6 at 52 weeks. Darbepoetin alpha showed similar efficacy in diabetics and non-diabetics. Patients switching from a high epoetin alpha dose (> or =4500 IU/week) had a higher conversion ratio compared with those switching from a low dose (<4500 IU/week).. The dose conversion ratio of 1:200 was unsuitable and led to a rapid increase of hemoglobin. A conversion ratio of 1:250 to 1:300 should be employed when switching from epoetin alpha to darbepoetin alpha in Japanese patients.

Topics: Aged; Anemia; Asian People; Biomarkers; Darbepoetin alfa; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Japan; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome

Topics: Anemia; Animals; Diabetes Mellitus; Erythropoietin; Humans; Kidney Diseases; Nephrons; Potassium Channels; Sodium-Glucose Transport Proteins

In patients with diabetes mellitus, hemoglobin A(1c) (A1C) is commonly interpreted as a measure of long-term glycemic control, reflecting a mean glucose level over the previous 2-3 months. Although some reports suggest that treatment with recombinant erythropoietin may affect A1C values in patients undergoing hemodialysis, we know of no evidence to support this interaction in patients with chronic renal insufficiency who are not undergoing hemodialysis. In addition, we know of no evidence specific to the treatment effect of epoetin alfa and/or darbepoetin alfa on A1C. We describe a 64-year-old man with diabetes, chronic kidney disease, and anemia who was treated consecutively with epoetin alfa and darbepoetin alfa and experienced a temporal reduction in A1C level to a nadir of 4.4%. Throughout approximately 3 years of treatment with these erythropoietin analogs, the patient's total daily dose of insulin was reduced in response to his decreasing A1C values, despite elevated blood glucose levels and the absence of patient-reported hypoglycemic events. Five months after the patient's erythropoietin therapy was discontinued, his A1C value increased to 8.8%, leading us to conclude that management of the insulin dose may have been different without the falsely lowered A1C levels. Use of the Naranjo adverse drug reaction probability scale indicated a probable association between this patient's reduced A1C levels and erythropoietin therapy. This case demonstrates that both epoetin alfa and darbepoetin alfa may artificially lower A1C levels in a patient with diabetes who is not undergoing dialysis, and therefore this finding can be interpreted as a class effect. Clinicians should be aware of factors that affect A1C values, specifically erythrocyte life span. In patients receiving erythropoietin, therapeutic decisions should be based on A1C and glucose levels, as well as patient symptoms suggestive of hypo- or hyperglycemia, to avoid therapy changes that could complicate disease management.

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus; Diabetic Nephropathies; Diagnostic Errors; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Glycated Hemoglobin; Hematinics; Humans; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic

Recent studies in mice experimental models with acute ischaemic injury revealed that erythropoietin (EPO) has numerous tissue-protective effects in the heart, brain and kidneys. We therefore explored the tissue-protective properties of chronic EPO treatment in an experimental model of the db/db mouse with diabetic heart injury.. We randomly treated 11 db/db mice with placebo (saline), 0.4 microg of the continuous erythropoietin receptor activator (CERA) per week (n = 11) or 1.2 microg CERA per week (n = 11) for 14 weeks, and analysed cardiac tissue. The lower CERA dose was a non-haematologically effective dose, whereas the second increased the haematocrit.. Compared with mice in the placebo group, CERA-treated mice had a reduction in TGF-beta(1) and collagen I expression in cardiac tissue (P < 0.01 vs. higher dose CERA). In addition, an increased expression of the pro-survival intracellular pathway p-AKT was observed (P < 0.05 vs. higher dose CERA). The values for the lower C.E.R.A had an intermediate nonsignificant effect. Furthermore, we were able to show that atrial natriuretic peptide (ANP) expression was increased in both CERA groups.. Chronic treatment with CERA protects cardiac tissue in diabetic animals, i.e. it inhibits molecular pathways of cardiac fibrosis, and the effects are dose-dependent.

Topics: Animals; Diabetes Mellitus; Diabetic Angiopathies; Dose-Response Relationship, Drug; Erythropoietin; Gene Expression Regulation; Immunohistochemistry; Male; Mice; Myocardium; Polyethylene Glycols; Recombinant Proteins

To investigate the relationship between Erythropoietin (EPO) and 1,25-dihydroxyvitamin D levels, and tubular damage in patients with diabetes mellitus (DM) without persistent microalbuminuria.. We measured serum EPO and 1,25-dihydroxyvitamin D levels and tubular injury markers such as urinary N-acetyl-beta-d-glucosaminidase (NAG) and retinol binding protein (RBP) levels in 41 non-diabetic controls, 40 patients with Type 1 and 40 with Type 2 DM.. Median serum EPO levels were lower in Type 1 (2.57 mIU/ml: p<0.001) and Type 2 DM (5.69 mIU/ml: p=0.044) than in controls (8.76 mIU/ml), though haemoglobin levels did not differ. Median 1,25-dihydroxyvitamin D levels were lower in Type 1 (41.0 pmol/l: p=0.001) and Type 2 DM (41.8 pmol/l: p=0.035) than in controls (56.1 pmol/l), though serum creatinine, calcium, phosphate and PTH levels did not differ. Median RBP excretion was higher in Type 2 DM (0.35 mg/l vs. 0.23 mg/l: p=0.013) than in controls. Median NAG excretion was higher in Type 1 DM (1,079 micromol/h vs.1,030 micromol/h: p=0.048) compared to controls.. Tubulo-interstitial damage with low levels of EPO and 1,25-dihydroxyvitamin D occurs early in Type 1 and Type 2 DM before persistent microalbuminuria.

Topics: Adult; Albuminuria; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Erythropoietin; Female; Glycated Hemoglobin; Humans; Kidney Tubules; Male; Middle Aged; Reference Values; Vitamin D; Young Adult

The purpose of this study was to evaluate erythropoietin (Epo) and Epo receptor (EpoR) expression in the retina and in vitreous fluid from diabetic and nondiabetic donors. To gain insight into the mechanisms responsible for the regulation of Epo production in the retina, we also assessed retinal expression of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha).. Eighteen postmortem eyes from 9 diabetic patients without clinically detectable retinopathy were compared with 18 eyes from 9 nondiabetic donors. mRNA of Epo, HIF-1alpha, and HIF-2alpha (quantitative RT-PCR) were measured separately in neuroretina and retinal pigment epithelium (RPE). Epo and EpoR were assessed in the retina (immunofluorescence by confocal laser microscopy) and in the vitreous fluid (radioimmunoassay and enzyme-linked immunosorbent assay, respectively).. Epo and EpoR mRNAs were significantly higher in the RPE than in the neuroretina. Higher expression of Epo was detected in the retinas (both in the RPE and in the neuroretina) from diabetic donors. By contrast, EpoR expression was similar in both groups. We did not find any difference in HIF-1alpha and HIF-2alpha mRNA expression between diabetic and nondiabetic donors (both in RPE and neuroretina). Intravitreal Epo concentration was higher in diabetic donors than in nondiabetic control subjects. However, EpoR concentrations were similar in both groups.. Epo overexpression is an early event in the retina of diabetic patients, and this is not associated with any change in EpoR. At this early stage, other factors apart from hypoxia seem to be more important in accounting for the Epo upregulation that exists in the diabetic retina.

Topics: Aged; Basic Helix-Loop-Helix Transcription Factors; Cadaver; Diabetes Mellitus; Erythropoietin; Glial Fibrillary Acidic Protein; Humans; Hypoxia-Inducible Factor 1; Microscopy, Confocal; Middle Aged; Pigment Epithelium of Eye; Receptors, Erythropoietin; Reference Values; Retina; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction

In 2007, several international studies brought useful information for the daily work of internists in hospital settings. This summary is of course subjective but reflects the interests and questions of the chief residents of the Department of internal medicine who wrote this article like an original trip in medical literature. This trip will allow you to review some aspects of important fields such as heart failure, diabetes, endocarditis, COPD, and quality of care. Besides the growing diversity of the fields covered by internal medicine, these various topics underline also the uncertainty internists have to face in a practice directed towards evidence.

Topics: Accidental Falls; Aged; Albuterol; Anemia; Anticoagulants; Antidiuretic Hormone Receptor Antagonists; Atrial Fibrillation; Attitude of Health Personnel; Benzazepines; Bronchitis, Chronic; Bronchodilator Agents; Cardiac Pacing, Artificial; Diabetes Mellitus; Endocarditis, Bacterial; Erythropoietin; Heart Failure; Heparin; Humans; Internal Medicine; Interprofessional Relations; Medical Staff, Hospital; Myocardial Infarction; Recombinant Proteins; Risk Management; Rosiglitazone; Salmeterol Xinafoate; Thiazolidinediones; Thromboembolism; Tolvaptan; Vasodilator Agents; Ventricular Dysfunction, Left; Workload

Anaemia is a common complication of renal impairment. It has been suggested that renal failure secondary to diabetes is associated with more severe anaemia, but this has not been clearly substantiated in the published literature. To clarify this, we undertook a single centre, retrospective study to identify the impact of diabetes on anaemia associated with renal impairment.. Information on clinical, biochemical and haematological parameters of 2,052 stable ambulatory patients attending a single tertiary referral renal unit was collected. The impact of diabetic kidney disease on haemoglobin levels at all degrees of renal impairment was studied by comparison with patients with non-diabetic kidney disease after correcting for other commonly associated variables that influence anaemia in patients with renal impairment.. Linear regression analysis showed lower haemoglobin in patients with diabetic kidney disease (p < 0.01). At chronic kidney disease (CKD) stages 3, 4 and 5, mean haemoglobin levels in patients with diabetic kidney disease compared with those in patients with non-diabetic kidney disease were 129.5 vs 136.9 g/l (p < 0.001), 120.5 vs 126.9 g/l (p < 0.001) and 107.1 vs 115.9 g/l (p < 0.01), respectively. At CKD stage 4 and 5 the two groups were comparable for ferritin, plasma intact parathyroid hormone levels, ACE inhibitor use and length of follow-up by a nephrologist.. Diabetic kidney disease is associated with lower haemoglobin in comparison with non-diabetic kidney disease, especially at GFR <60 ml/min.

Topics: Anemia; Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Erythropoietin; Female; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Regression Analysis; Retrospective Studies

Epidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged > or =65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36.8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non-anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro-inflammatory markers and low lymphocyte counts.

Topics: Aged; Aging; Anemia; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Erythropoietin; Female; Health Surveys; Humans; Inflammation Mediators; Interleukin-6; Italy; Kidney Diseases; Lymphocyte Count; Male; Osteoarthritis; Parkinson Disease; Stroke; Tumor Necrosis Factor-alpha

In the present study, we aimed to determine levels of free carnitine in hemodialysis (HD) and peritoneal dialysis (PD) patients in India and to correlate carnitine deficiency with various clinical parameters.. Patients on HD and PD at two tertiary care centers were selected for the study. Baseline data were obtained, and a free carnitine analysis was performed. Carnitine deficiency was defined as a free carnitine level of less than 40 micromol/L.. The total number of study patients was 96 (77 on HD, 19 on PD). In the PD group, the mean age was 56 years, with 26.3% of the patients being vegan, 47.4% having diabetes, and 57.9% having a daily urine output of <500 mL. The mean carnitine level in that group was 38.9 micromol/L, and 68.4% of the patients had a carnitine deficiency. A Pearson correlation test failed to show any association of carnitine level with parameters such as anemia, use of erythropoietin, non-vegetarian diet, diabetes, and hypertension. In the HD group, the mean age was 45 years, with 22% of the patients being vegan, 23% having diabetes, and 45.5% having a daily urine output of <500 mL. The mean carnitine level in the group was 38.2 micromol/L, and 64.3% of the patients had a carnitine deficiency. Residual renal function and duration of dialysis were different in HD patients with and without carnitine deficiency. Carnitine levels in the HD group correlated positively and statistically significantly with the presence of diabetes and hypertension.. This study is the first demonstration that Indian dialysis patients have carnitine deficiency.

Topics: Adult; Aged; Anemia; Carnitine; Chi-Square Distribution; Diabetes Mellitus; Erythropoietin; Female; Humans; India; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Topics: alpha-Fetoproteins; Amino Acid Sequence; Animals; Biomarkers; Biopharmaceutics; Diabetes Mellitus; Erythropoietin; Fibrinogen; Glycopeptides; Mice; Proteomics; Recombinant Proteins

Diabetes mellitus is associated with an increased prevalence of anemia, particularly in patients with nephropathy. We undertook this survey to determine the relationship between anemia and the renal production of erythropoietin in patients with diabetes mellitus.. The clinical data of 722 patients were obtained, including markers of diabetic complications. Erythropoietin levels were measured in the same samples. Patients with a full blood cell count, iron indexes, and renal function within the normal range (n = 151) were used to define the reference range for this population. Anemic patients who had erythropoietin levels within this range were defined as having an "inappropriate erythropoietin response to anemia.". Of the 722 patients, 168 (23.3%) had anemia, of whom 130 (77.4%) had erythropoietin levels inappropriately within the normal range. Although 55.4% of anemic patients had moderate renal impairment, erythropoietin levels were also inappropriately low in 69.2% of anemic patients with normal renal function. However, most of these patients (17 of 26) had diabetic kidney disease, as denoted by albuminuria.. The failure to produce erythropoietin in response to a declining hemoglobin level is a common contributor to anemia in patients with diabetes mellitus. This seems to be a manifestation of diabetic kidney disease, in the presence or absence of renal impairment.

Topics: Aged; Albuminuria; Anemia; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Female; Follow-Up Studies; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney; Male; Middle Aged; Multivariate Analysis

It is unknown whether traditional cardiovascular disease risk factors influence the number of endothelial progenitor cells (EPCs) and whether numbers of EPCs correlate with endothelial function in patients with end-stage renal disease.. In a cross-sectional study of 38 peritoneal dialysis patients, we examined numbers of circulating CD34+/KDR+/CD133+ cells, CD34+ hematopoietic stem cells, and EPCs cultured from peripheral blood. We also assessed conventional cardiovascular disease risk factors, such as history of vascular disease, diabetes, hypercholesterolemia, hypertension, and smoking. We determined endothelial function by measurement of endothelium-dependent and endothelium-independent reactivity of forearm resistance arteries by using strain-gauge plethysmography.. Numbers of EPCs cultured from peripheral blood and forearm blood flow reactivity did not differ between erythropoietin-treated peritoneal dialysis patients and healthy individuals. A history of vascular disease was associated with number of cultured EPCs, but other cardiovascular disease risk factors showed no association. Furthermore, there was no association of endothelial-dependent and endothelial-independent forearm blood flow reactivity with EPCs in peritoneal dialysis patients.. In this first study of EPCs in peritoneal dialysis patients, we found an association between history of vascular disease and EPCs, but no association of EPCs with endothelial function or other cardiovascular disease risk factors.

Topics: Aged; Anemia; Antigens, CD; Blood Cell Count; Blood Flow Velocity; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Endothelial Cells; Endothelium, Vascular; Erythropoietin; Female; Forearm; Hematopoietic Stem Cells; Humans; Hypercholesterolemia; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Risk Factors; Smoking; Vascular Resistance

The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

Topics: Animals; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Erythrocyte Count; Erythropoietin; Female; Glycated Hemoglobin; Hemoglobins; Humans; Leptin; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1; Recombinant Proteins; RNA, Messenger; Skin; Vascular Endothelial Growth Factor A; Wound Healing; Wounds and Injuries

One of the complications of hemodialysis (HD) therapy is anemia caused by erythropoietin (EPO) deficiency. Recombinant EPO (rEPO) has been used routinely as a supplemental treatment. Erythrocyte expression of the complement regulatory proteins decay accelerating factor (DAF) and CD59 restricts complement activation and inhibits hemolysis. We hypothesized that the efficacy of rEPO treatment may be caused in part by the ability of rEPO to increase erythrocyte expression of DAF and CD59.. DAF, CD59, and complement receptor 1 (CR1) levels were analyzed for a group of 95 HD patients and compared with those of a control group. To evaluate effects of discontinuation of rEPO therapy, rEPO therapy was stopped for 12 HD patients until hematocrits decreased to less than 25%. DAF and CD59 levels then were reanalyzed.. In the 95 HD patients, three factors correlated significantly: DAF and CD59 (r = 0.642), DAF and CR1 (r = 0.503), and CD59 and CR1 (r = 0.324), whereas no correlations were found in the group of 42 healthy controls. In the experiment in which rEPO therapy was discontinued, 8 of 12 patients reached the defined level of anemia 4 to 7 weeks after rEPO treatment had been withheld. Both DAF and CD59 levels decreased significantly after discontinuation of rEPO therapy (P < 0.01). DAF and CD59 levels increased in all 8 patients after rEPO treatment was reinitiated (P < 0.01), and CR1 levels increased in 5 of 8 patients. Four of 12 patients showed no evidence of anemia after discontinuation of rEPO treatment. In these patients, DAF, CD59, and CR1 levels did not change before or after withholding rEPO therapy.. One of the mechanisms mediating the efficacy of EPO therapy is increased DAF and CD59 expression.

Topics: Anemia; CD55 Antigens; CD59 Antigens; Chronic Disease; Complement C3; Diabetes Mellitus; Erythrocytes; Erythropoietin; Glomerulonephritis; Humans; Middle Aged; Receptors, Complement; Recombinant Proteins; Renal Dialysis; Renal Insufficiency

Secondary hyperparathyroidism is a common complication of renal failure. The exact prevalence in chronic hemodialysis patients in not known. We evaluated 122 patients who were receiving maintenance hemodialysis for at least 12 months in 2 dialysis centers in mid Michigan. Seventy-eight percent of the patients had iPTH above 200 pg/mL (mean 481 pg/mL), 19% had iPTH within the accepted normal range (mean 155 pg/mL), while 3% had level below 100 (mean 53 pg/mL). Phosphate, calcium, calcium phosphate product, age and time on dialysis are the important factors correlating with elevated iPTH. There was no significant difference in iPTH between diabetic and nondiabetic patients with mean iPTH of 403 pg/mL and 407 pg/mL respectively. Black patients had a statistically significant elevated iPTH compared with white patients with a mean iPTH of 438 pg/mL and 283 pg/mL respectively (p < or = 0.004). Factors that predict the response to vitamin D therapy need to be evaluated to help reduce the high prevalence of secondary hyperparathyroidism. The patterns of bone disease in black patients need to be evaluated to further define the accepted normal iPTH range for this population.

Topics: Adult; Age Factors; Calcium Phosphates; Diabetes Complications; Diabetes Mellitus; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Hypertension; Kidney Failure, Chronic; Male; Michigan; Middle Aged; Parathyroid Hormone; Prevalence; Racial Groups; Recombinant Proteins; Renal Dialysis; Statistics as Topic; Time Factors; Urea

Anemia is a common complication of advancing chronic kidney disease, yet little is known about the consistency of anemia treatment before end-stage renal disease (ESRD) and mortality on dialysis therapy.. We studied 89,193 incident Medicare patients with ESRD in 1995 to 1997 aged 67 plus years with claims 2 years before their dialysis therapy initiation. Patients were classified as follows: no epoetin, 25% or less (least consistent), greater than 25% to 50%, greater than 50% to 75%, and greater than 75% (most consistent) epoetin treatment in the available months from the first pre-ESRD epoetin dose to the first ESRD service date. Cox regression modeled the risk for 1-year death in the post-ESRD period, adjusting for age, sex, race, diabetic status, albumin level, and incidence year.. Sixty percent of patients had hematocrits less than 30% at ESRD initiation, yet only 15.6% (N = 13,877) had epoetin claims before ESRD. The most consistent epoetin treatment group had hematocrits increase from 27.5% to 30.8% (P < 0.0001) by month 4 of treatment. Patients with the most consistent epoetin treatment had a greater mean hematocrit (29.2% +/- 0.11%; P < 0.0001) and albumin level (3.31 +/- 0.01 g/dL [33.1 g/L]) at initiation than those with the least consistent treatment (28.1% +/- 0.10% and 3.21 +/- 0.01 g/dL [32.1 g/L], respectively). The relative risk for death in patients with the least consistent versus the most consistent (the reference) epoetin treatment was 1.460 (95% CI, 1.245 to 1.713; P < 0.0001) 1 year after the first ESRD service date.. Elderly patients with consistent pre-ESRD epoetin treatment had lower risks for death in the first year of dialysis therapy after ESRD initiation.

Topics: Aged; Anemia; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Models, Statistical; Mortality; Racial Groups; Recombinant Proteins; Renal Dialysis; Reproducibility of Results; Serum Albumin; Sex Factors; Survival Rate

Peritoneal dialysis (PD) patients have been shown to require less erythropoietin as compared with hemodialysis (HD) patients to maintain similar hemoglobin values. In our unit, we observed that diabetic PD patients required less erythropoietin treatment than did other PD patients. We therefore compared the amount of erythropoietin needed in diabetic and non diabetic patients on PD to maintain a similar hemoglobin value. All polycystic patients were excluded from the study because they rarely require erythropoietin. We also excluded patients with bone marrow disease, active gastrointestinal bleeding, or patients very resistant (requiring more than 25,000 U per week) to Eprex (recombinant human erythropoietin: Janssen-Cilag, North York, Ontario, Canada). Patients not requiring Eprex were also excluded from the study. We calculated the weekly erythropoietin dose in the two groups. We also compared hemoglobin level, iron transferrin saturation, vitamin?12 level, and serum folate. Diabetic patients required a lower weekly erythropoietin dose. Diabetic PD patients in our unti receive an average 4497 U per week compared with 7593 U per week for non diabetic PD patients. The difference (approximately 3000 U per week) is statistically significant.

Topics: Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Folic Acid; Hemoglobins; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis; Transferrin; Vitamin B 12

The aim of the present study was to examine the association between 4-hour dialysate-to-plasma ratio of creatinine (D/PCr), erythropoietin (EPO) responsiveness [EPO (U/week)/hemoglobin (g/L)], and C-reactive protein (CRP). Subjects were 54 prevalent peritoneal dialysis (PD) patients [mean age: 58 years; 30 women, 24 men; 28 with diabetes; 15 on continuous ambulatory peritoneal dialysis (CAPD); 39 on continuous cycling peritoneal dialysis (CCPD); mean Kt/V: 2.44]. In 17 patients, CRP was elevated (> 15 mg/L), and in 39 patients, 4-hour D/PCr was high or high-average (> or = 0.65). Mean hemoglobin (Hb) was 115.5 +/- 12.9 g/L; median EPO dose was 2800 U/week, and median EPO/Hb was 24.5. A nonsignificant negative correlation was noted between CRP and hemoglobin (r = -0.25, p = 0.07), but no correlations were seen between CRP and 4-hour D/PCr, or hemoglobin and 4-hour D/PCr. No correlation was seen between EPO/Hb and 4-hour D/PCr or CRP. Multiple linear regression (stepwise, alpha = 0.05) was performed with outcome hemoglobin and independent variables EPO [U/week (forced in)], percent transferrin saturation [TSAT (forced in)], age, sex, diabetes mellitus, serum albumin, CRP, time on PD, 4-hour D/PCr, normalized protein catabolic rate (nPCR), ferritin, intact parathyroid hormone (iPTH), aluminum, and angiotensin converting enzyme inhibitor (ACEI) use. Serum albumin (1.27, p < 0.01) and diabetes mellitus (-6.69, p = 0.04) were the only significant predictors of hemoglobin. With serum albumin removed from the model, age (but not CRP) became significant. These results do not support an association between peritoneal transport and EPO responsiveness, mediated by inflammation. The association between serum albumin and hemoglobin appears to be confounded by age more than by inflammation.

Topics: Biological Transport; C-Reactive Protein; Creatinine; Diabetes Mellitus; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Proteins; Regression Analysis

The present study looked for variations in blood morphology between diabetic patients (group I, n = 7) and non diabetic patients (group II, n = 16) treated with continuous ambulatory peritoneal dialysis (CAPD). A subsequent trial sought to find a reason for discrepancies in the results between the two groups. The patients in both groups and similar ages, CAPD durations, and erythropoietin dosages. Nutrition, CAPD adequacy, serum iron and ferritin levels, total iron binding capacity (TIBC), transferrin saturation (TSAT), red blood cells (RBCs), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb), hematocrit (Hct), white blood cells (WBCs), total lymphocyte count (TLC), platelets (PLTs), and serum intact parathyroid hormone (PTH) were evaluated every three months. The mean result of each parameter was obtained in every patient as representative for the entire CAPD course. Means and standard deviations for all respective parameters were then calculated for the two groups and compared. In patients with diabetes as compared with patients without diabetes, significantly higher numbers of RBCs, WBCs, and PLTs were seen, as were higher values for Hb and Hct and a lower serum PTH concentration. Values for WBCs, PLTs, and MCH obtained in all patients (n = 23) were correlated with serum intact PTH (r = -0.520, p = 0.011; r = -0.422, p = 0.045; and r = -0.436, p = 0.037 respectively). When data obtained in the patients receiving erythropoietin were excluded and the correlation analysis was repeated for the 10 remaining patients, a correlation between serum PTH and RBCs was found (r = -0.685, p = 0.029). With comparable age, renal function, nutrition, erythropoietin dosage, iron indices, and CAPD adequacy, duration, and outcome, higher parameters of blood morphology in diabetic patients may be related to lower levels of serum intact PTH, indicating no or only mild secondary hyperparathyroidism. Patients with diabetes usually show smaller disturbances in PTH level than do non diabetic uremic patients on CAPD. Better peripheral morphology indices in the group with diabetes can be expected when other factors affecting hematologic status are similar.

Topics: Adult; Blood Cell Count; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Parathyroid Hormone; Peritoneal Dialysis, Continuous Ambulatory; Retrospective Studies

Several investigators reported that individuals with diabetes and women on hemodialysis treated with recombinant erythropoietin (EPO) attained lower hematocrits than individuals without diabetes and men. It is unclear whether these observed differences in achieved hematocrits are caused by inherent biological differences in responsiveness to EPO or undetected differences in modifiable factors that affect response to EPO. Also potentially modulating response to EPO is diurnal variation in the bioavailability of serum iron. To address these issues, we studied 309 patients undergoing hemodialysis in two large facilities in New York City. Retrospective data collected monthly for 3 months included patients' hematocrit, dose of EPO, urea reduction ratio (URR), total amount of intravenous iron administered, serum albumin concentration, transferrin saturation, and time of day patient underwent dialysis. The 309 study subjects (165 women, 144 men) included 207 blacks (67%), 74 Hispanics (24%), 23 whites (7%), and 5 Asians (2%) with a mean age of 55.4 +/- 15.6 (SD) years. Despite a greater mean URR (74% +/- 6.4% versus 71% +/- 6%; P = 0.001) and a 39% greater dose of EPO (97 +/- 65 versus 59 +/- 53 U/kg; P = 0.001), women (36% +/- 3.5%) had hematocrits equivalent with men (36.5% +/- 3.7%; P = not significant [NS]). There was no difference in the amount of intravenous iron administered to men (375 +/- 389 mg) and women (377 +/- 413 mg; P = NS). Diabetes mellitus (P = 0.48) did not significantly affect the odds of attaining a hematocrit greater than 33% after adjustment for URR, EPO dose, and amount of intravenous iron administered. The time of day a patient underwent dialysis (P = 0.93) had no effect on their response to EPO. We conclude that gender, but not diabetes status or time of dialysis, modulates response to EPO in hemodialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Black People; Circadian Rhythm; Confidence Intervals; Diabetes Mellitus; Erythropoietin; Female; Hematocrit; Hispanic or Latino; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Renal Dialysis; Retrospective Studies; Sex Factors; White People

We often encounter diabetic patients with anemia in whom the causes of anemia were not clearly identified despite differential hematologic studies. We therefore studied the clinical and biochemical characteristics of diabetic patients with anemia of uncertain cause and measured erythropoietin (Epo) concentrations in 35 diabetic subjects without significant diabetic renal disease. Among 62 medical records of diabetic patients with anemia, showing no evidence of advanced diabetic nephropathy (creatinine clearance > or = 30 mg/kg/1.73 m2), the causes of the anemia were not able to be identified in 28 cases (45.2%). In addition, we enrolled 35 diabetic patients with uncertain causes of anemia in order to evaluate the serum Epo responsiveness to anemia, and compared levels to a group of non-diabetic subjects also with anemia. The serum Epo concentrations of diabetic patients (17.6 +/- 8.1 mIU/ml) were significantly lower than those of non-diabetic patients with similar degree of decrease in hemoglobin concentrations (144.9 +/- 108.0 mIU/ml, P<0.001). The hemoglobin concentrations of diabetic patients correlated with creatinine clearance (r = 0.34, P = 0.03), serum creatinine (r = -0.49, P = 0.003) and albumin excretion rate (r = -0.44, P = 0.009), but showed no relation to age, duration of diabetes, glycated hemoglobin, presence of retinopathy or neuropathy. We concluded that reduced Epo responsiveness to anemia could explain the anemia present in diabetic patient but without advanced diabetic nephropathy. This may reflect early renal interstitial damage.

Topics: Aged; Anemia; Creatinine; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged

Despite the prevalent use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients. The goal of this study was to evaluate the impact of anemia on patient survival and characterize the determinants of hematopoiesis that may be amenable to therapeutic manipulation to enhance rhEPO responsiveness and reduce death risk. Patient characteristics and laboratory data were collected for 21,899 patients receiving hemodialysis three times per week in dialysis centers throughout the United States in 1993. Hemoglobin concentrations (Hb) < or =80 g/L were associated with a twofold increase in the odds of death (odds ratio = 2.01; P = 0.001) when compared with Hb 100 to 110 g/L. No improvement in the odds of death was afforded for Hb >110 g/L. Using multiple linear regression, variables of rhEPO administration (rhEPO dose and percentage of treatments that rhEPO was administered), variables of iron status (serum iron, transferrin saturation, and ferritin), variables of nutritional status (serum albumin and creatinine concentration), and the dose of dialysis (urea reduction ratio) were found to be significantly associated with hemoglobin concentration (P < 0.001). Age, race, and gender were also found to be significantly associated with hemoglobin concentrations (P < 0.001). From this report, the following conclusions may be made. (1) Anemia may be predictive of an increased risk of mortality in some hemodialysis patients. (2) Hemoglobin concentrations > 110 g/L are not associated with further improvements in the odds of death. (3) Laboratory surrogates of iron stores, nutritional status, and the delivered dose of dialysis are predictive of hemoglobin concentration. Whether manipulation of the factors that improve anemia will also enhance the survival of patients on hemodialysis is unknown and should be evaluated by prospective, interventional studies.

Topics: Adult; Aged; Anemia; Anemia, Hypochromic; Comorbidity; Creatinine; Diabetes Mellitus; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Nutrition Disorders; Odds Ratio; Predictive Value of Tests; Prevalence; Recombinant Proteins; Regression Analysis; Renal Dialysis; Risk Factors; Serum Albumin; Survival Analysis; Transferrin; Treatment Outcome; United States

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Topics: Aged; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Erythropoietin; Ferritins; Hemochromatosis; Humans; Iron; Iron Overload; Islets of Langerhans; Male; Phlebotomy; Recombinant Proteins

Recombinant human erythropoietin is widely used in chronic dialysis patients. However, the long-term effect, especially on the incidence of cardiovascular disease, has not been critically evaluated. We observed the annual incidence of stroke and acute myocardial infarction from April 1988 through March 1993 in Okinawa, Japan. Until April 1990, erythropoietin was not generally used. Therefore, we have two periods: pre-erythropoietin, April 1988 through March 1990, and post-erythropoietin, April 1990 through March 1993. Two thousand one hundred and sixteen patients (1,219 males and 897 females) were on chronic dialysis during the study period by March 31, 1993. Every case of stroke and acute myocardial infarction during the study period was registered. The odds ratio was calculated using the data of the general population in each sex and age class obtained in the same area. A total of 86 cases of stroke and 15 cases of acute myocardial infarction were registered during the study period. The annual incidence, per 1,000 patient-years, of stroke was 12.5 (1988), 10.5 (1989), 12.7 (1990), 14.0 (1991), and 17.5 (1992). The incidence of stroke was increased in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.22 and 95% confidence interval (95% CI 1.06-1.41, p < 0.01). The annual incidence of acute myocardial infarction was 1.0 (1988), 1.8 (1989), 0.8 (1990), 2.9 (1991) and 4.7 (1992). The incidence of acute myocardial infarction was increased significantly in the post-erythropoietin period compared to the pre-erythropoietin period, odds ratio 1.87 (95% CI 1.66-2.10, p < 0.01). The odds ratio of stroke to the general population was 4.25 (95% CI 3.10-5.82) in the pre-erythropoietin and 4.58 (95% CI 2.14-9.80) in the post-erythropoietin period. In acute myocardial infarction, it was 2.98 (95% CI 2.84-3.12) and 3.81 (95% CI 3.18-4.56). The odds ratio of acute myocardial infarction was significantly increased (p < 0.01). The introduction of erythropoietin was associated with an increased risk of cardiovascular disease, especially acute myocardial infarction. Erythropoietin may unmask the sclerotic lesion in chronic dialysis patients.

Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Diabetes Mellitus; Erythropoietin; Female; Humans; Japan; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Risk Factors

Transdermal drug delivery offers a potential method of drug administration. However, its application has been limited to a few low molecular weight compounds because of the extremely low permeability of human skin. Low-frequency ultrasound was shown to increase the permeability of human skin to many drugs, including high molecular weight proteins, by several orders of magnitude, thus making transdermal administration of these molecules potentially feasible. It was possible to deliver and control therapeutic doses of proteins such as insulin, interferon gamma, and erythropoeitin across human skin. Low-frequency ultrasound is thus a potential noninvasive substitute for traditional methods of drug delivery, such as injections.

Topics: Administration, Cutaneous; Blood Glucose; Diabetes Mellitus; Epidermis; Erythropoietin; Humans; Insulin; Interferon-gamma; Permeability; Phonophoresis; Proteins; Skin Absorption; Transducers

Outcomes goals in managing anemia in end-stage renal disease (ESRD) with epoetin alfa and other therapies are illustrated with a case study. Anemia is common in patients with ESRD undergoing hemodialysis; the cause is primarily a reduction in the secretion of erythropoietin. Multiple coexisting factors, such as iron deficiency and blood loss, also contribute. Outcomes goals include decreasing blood transfusions, increasing physical performance, improving cardiovascular and cognitive function, enhancing overall well-being, and achieving self-sufficiency. The potential to achieve these goals has been linked to the attainment of an optima, hematocrit and hemoglobin concentration with epoetin alfa therapy. Once epoetin alfa is begun, safety and effectiveness should be monitored and attainment of outcomes goals assessed. Supplemental iron, folate, and cyanocobalamin may be necessary, as may management of the underlying inflammatory process. The pharmacist can help optimize outcomes by conducting drug-use evaluations, monitoring laboratory test values and drug dosages, assessing drug effectiveness, and counseling patients. A case study of a 67-year-old woman with diabetes mellitus and ESRD who was placed on hemodialysis is presented as an example of how the pharmacist can help optimize outcomes. Opportunities for pharmacists in outcomes management in patients with ESRD-associated anemia include monitoring epoetin alfa therapy, counseling patients, and working with the renal team.

Topics: Aged; Anemia; Diabetes Complications; Diabetes Mellitus; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Outcome Assessment, Health Care; Patient Education as Topic; Pharmacists; Renal Dialysis; United States

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.

Topics: Age Factors; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Canada; Cardiomyopathies; Cohort Studies; Comorbidity; Diabetes Mellitus; Echocardiography; Erythropoietin; Female; Hematocrit; Humans; Hyperlipidemias; Hyperparathyroidism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Smoking; Survival Analysis; Systole

The objective was to evaluate the effect of the treatment of anemia with recombinant human erythropoietin (EPO) on thrombosis of the vascular access used for hemodialysis. The research design was a prospective cohort study comparing EPO-treated hemodialysis patients with a comparison group matched for type of vascular access, clinical center, and age. All patients commencing hemodialysis in the study centers between March 1988 and July 1991 were eligible if either a graft or fistula had been used as a first permanent vascular access. There were 64 matched fistula pairs and 38 matched graft pairs. There were more patients with a history of cardiovascular disease in the EPO group than in the comparison group for both fistulae and grafts, 34 versus 14% for the former and 37 versus 5% for the latter. There was no difference between EPO and comparison groups with respect to time to first thrombosis of fistula, 11.3 versus 10.6%, respectively, by thrombosis of grafts among those treated with EPO--33.6 versus 11.2% (P = 0.02). EPO treatment does not increase the probability of fistula thrombosis, but there is an association with an increased probability of graft thrombosis.

Topics: Actuarial Analysis; Adolescent; Adult; Aged; Anemia; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis; Cardiovascular Diseases; Catheters, Indwelling; Cohort Studies; Comorbidity; Diabetes Mellitus; Erythropoietin; Female; Humans; Immunologic Factors; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Serum Albumin; Thrombosis

To assess the extent of functional and vocational rehabilitation achieved by elderly inner-city patients sustained on maintenance hemodialysis.. Inception cohort study of elderly patients who have end-stage renal disease using a modified Karnofsky rating system. The need for a wheelchair, participation in household activities, and effect of comorbid conditions were noted. Current status was compared with patient's recollection of functional activity level 2 years before commencing maintenance hemodialysis.. Seven outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY.. One hundred four patients aged 65 years or older who were receiving maintenance hemodialysis for at least 6 months.. A score of 76 or greater on a modified Karnofsky scale indicated independent function at a level that permitted participation in activities beyond those mandated by the hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed index correlated with severe debility. Employment status was also recorded.. Present functional activity had deteriorated to a modified Karnofsky score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis. Diabetic patients had a lower score than nondiabetic patients. The mean comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within the diabetic subset, severe debility constrained 71 patients (68%) to limit all activity to their residence with the exception of travel to and from their dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81 diabetic patients (78%) had interests and activities that took them outside their homes (P < .001). Generalized weakness was the most common explanation given for the lack of outside activity by nine patients (9%) who were wheelchair bound. Erythropoietin, though regularly administered to 87 patients (84%) in the study group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05 (mean +/- SD).. Maintenance hemodialysis does not return inner-city elderly patients to their predialysis level of functioning. Few elderly, diabetic hemodialysis patients conduct any substantive portion of their lives outside their homes. For nondiabetic patients, the modified Karnofsky score of whites (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4).

Topics: Activities of Daily Living; Age Factors; Aged; Aged, 80 and over; Black People; Cohort Studies; Comorbidity; Diabetes Mellitus; Erythropoietin; Female; Humans; Karnofsky Performance Status; Kidney Failure, Chronic; Male; New York City; Outcome Assessment, Health Care; Renal Dialysis; Sex Factors; Time Factors; Urban Population; White People

Our purpose was to investigate the relationship between fetal plasma erythropoietin concentration and measures of short-term and long-term glycemic control and fetal oxygenation in pregnancies complicated by maternal diabetes mellitus.. A cross-sectional study was performed at The Harris Birthright Research Centre for Fetal Medicine, London. Cordocentesis was performed in 31 diabetic pregnancies for the measurement of umbilical venous blood pH, PO2, PCO2, lactate and glucose concentration, erythroblast count, hemoglobin, and plasma erythropoietin concentrations.. The mean pH was significantly lower and the PCO2, lactate, erythropoietin, hemoglobin, and erythroblast counts were significantly higher than the appropriate normal mean for gestation. There were significant associations between (1) fetal erythropoietin and erythroblast count, (2) fetal erythroblast count and hemoglobin, (3) fetal hemoglobin and maternal glycosylated hemoglobin, and (4) maternal glucose and fetal glucose, pH, and lactate.. We postulate that maternal hyperglycemia causes fetal hyperglycemia and acidemia. Increased erythropoietin may be caused by tissue hypoxia or hyperinsulinemia. The increase in fetal hemoglobin may be the consequence of increased erythropoiesis, mediated by either erythropoietin or hyperinsulinemia.

Topics: Diabetes Mellitus; Diabetes, Gestational; Erythrocyte Count; Erythropoietin; Female; Fetal Blood; Glycated Hemoglobin; Humans; Pregnancy; Pregnancy in Diabetics

Serum erythropoietin (EPO) levels were determined by the recombigen EPO RIA kit (DPC) in normal subjects and patients with renal dysfunction, diabetes mellitus, hypothyroidism and a variety of hematological disorders. Mean (+/- SD) serum EPO levels were 18.6 +/- 5.6 mU/ml in 180 normal subjects and no sex difference was obtained. Serum EPO levels in older subjects were slightly greater than those in younger subjects. There was a negative correlation between serum EPO levels and Ht values in anemic patients with normal renal function, whereas serum EPO levels were within the normal range in anemic patients with renal disorders, suggesting that serum EPO levels were relatively low in patients with chronic renal failure. Serum EPO levels were rather increased in patients with diabetes mellitus and hypothyroidism. High serum EPO levels were obtained in patients with a variety of hematological disorders such as acute leukemia, multiple myeloma, myelodysplasia syndrome, aplastic anemia and pure red cell aplasia. In a patient with pure red cell aplasia treated with glucocorticoids, serum EPO levels were lowered before anemia was recovered and reticulocytes were increased. These findings indicate that measurement of serum EPO levels are useful for not only differential diagnosis of anemia but also clinical evaluation of the treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Diabetes Mellitus; Erythropoietin; Female; Humans; Male; Middle Aged; Reagent Kits, Diagnostic; Red-Cell Aplasia, Pure; Reference Values

The pathogenesis of the increased erythrocytosis and extramedullary erythropoiesis observed in infants of diabetic mothers (IDM) has been obscure. In the present studies, IDM were found to have elevated umbilical plasma erythropoietin (Ep) concentrations by radioimmunoassay. 22 of 61 IDM (36%) had levels above the range of 28 nonasphyxiated, appropriately grown normal infants. In 16 controls and 20 IDM, plasma Ep correlated directly with plasma insulin (P less than 0.001, r = 0.73). To investigate this relationship further, a chronic rhesus model was studied with continuous fetal hyperinsulinemia for 21 d in utero in the last third of pregnancy. In five experimental fetuses, plasma insulin levels averaged 4,210 microU/ml at delivery, whereas plasma Ep was above the range of six controls. In addition, the experimental fetuses had elevated reticulocyte counts in umbilical cord blood. The mechanism for the increased plasma Ep associated with hyperinsulinemia in the fetus is unexplained but may be mediated by fetal hypoxia.

Topics: Animals; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Disease Models, Animal; Erythropoiesis; Erythropoietin; Female; Fetal Blood; Hemoglobin A; Humans; Hyperinsulinism; Insulin; Macaca mulatta; Pregnancy; Pregnancy in Diabetics

The regulation of erythropoiesis in 40 subjects with diabetes mellitus was investigated to test the hypothesis that increased blood concentrations of glycosylated hemoglobin would produce a reduced p50 and a compensatory increase in erythropoietin. Little evidence to support this hypothesis was observed. However, diabetes did produce complex changes in hemoglobin-oxygen releasing capacity which were compensated for in the expected way, i.e. oxygen releasing capacity showed an inverse correlation with erythropoietin. We conclude that the effects of diabetes on erythropoiesis are minor and probably have no pathological significance in most patients suffering from this disease.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Erythropoiesis; Erythropoietin; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Oxygen