A prospective observational study on the effect of Erythropoiesis stimulating agents in chronic kidney disease Anemia patients

Background and Objectives: Anemia is a frequent complication, and significant morbidity and mortality in patient with chronic kidney disease (CKD). Erythropoiesis Stimulating Agents (ESAs) have become the standard care for anemia t erapy and reduces need for blood transfusions. The bjective of the study was to evaluate the safety and effect of ESAs and to create the awareness among patients regarding the Erythropoiesis stimulating agents through patient i formation leaflets.Methods: The prospective observational study of 6-month duration was conducted in a tertiary care hospital. A total of 162 patients on ESAs were enrolled in the study. Patients were followed for continuously and the mean difference is assessed by monitoring the primary and secondary hematological parameters before and after ESAs administration. Patient information leaflet was given t the patients for education and awareness about ESAs.Results: Out of 162 patients, after the administration of ESAs mean value increase in hemoglobin level was found from base line 6.9g/dL to 11.6g/dL. Significant improvement was noted in CKD anemia patient indicating impact of patient counseli g.Conclusion: It can be concluded that Erythropoiesis Stimulating Agents in treatment of anemia along with effective counseling from clinical pharmacist benefits CKD patients and improves the health outcomes.

Obesity may be erythropoietin dose-saving in hemodialysis patients

BACKGROUND: In dialysis patients, the obesity-survival paradox still requires an explanation. Anemia and high doses of erythropoiesis-stimulating agents (ESAs) are associated with worse outcomes in the hemodialysis (HD) population. In the present study, we explored the relation between obesity and anemia control in a sample of maintenance HD patients in Egypt. METHODS: This multicenter observational study included 733 patients on maintenance HD from 9 hemodialysis centers in Egypt. Clinical and laboratory data as well as average doses of ESAs and parenteral iron were recorded. The erythropoietin resistance index (ERI) was calculated. RESULTS: Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, was present in 22.6% of the studied population. The target hemoglobin level (10.0–11.5 g/dL) was achieved in 27.3% of non-obese and 25.3% of obese patients, with no significant difference. The median serum ferritin and the values of transferrin saturation index did not differ significantly between these two groups. The weekly ESA dose was significantly lower in obese than in non-obese patients (P = 0.0001). A trend toward higher ESA doses and ERI values was observed in patients with lower BMIs (P < 0.0001). Multiple linear regression revealed that the BMI and urea reduction ratio were the strongest predictors of the ERI. CONCLUSION: Our study adds more evidence to obesity-associated advantages in HD patients. BMI may determine ESA response, with better responses observed in patients with higher BMIs.

Administration of a High-Dose Erythropoietin-Stimulating Agent in Hemodialysis Patients is Associated with Late Arteriovenous Fistula Failure

PURPOSE: Investigating the risk of vascular access failure is critical for maintenance hemodialysis (MHD) patients. Erythropoietin stimulating agents (ESA) typically used for anemia of chronic kidney disease (CKD) may also stimulate neointimal hyperplasia, which is the most important factor in late arteriovenous fistula (AVF) failure. The aim of this study was to investigate whether ESA treatment is associated with late AVF failure. MATERIALS AND METHODS: The late AVF failure group comprised 51 patients who underwent percutaneous intervention or surgery for fistula revision after successful use for at least three months. There were 51 controls whose AVF had been patent for at least 24 months. RESULTS: The mean time from the first cannulation to late loss of AVF patency was 8.4±4.2 months. The average weekly dose of ESA was significantly higher in patients with AVF failure (4782.2±2360.5 IU/mL/wk vs. 7161.8±2775.2 IU/mL/wk, p<0.001). The only independent predictor of late AVF failure in multivariate analysis was high average ESA dose (odds ratio=1.015, 95% confidence interval=1.002–1.028, p=0.022). CONCLUSION: Patients with late AVF patency loss exhibit an association with a higher dose of ESA, although causality is unproven. Further study to elucidate potential mechanisms is warranted.

Chronic kidney disease-associated anemia: Progress in treatment / 第二军医大学学报

Chronic kidney disease(CKD)-associated anemia is developed during CKD; it is one of the important clinical manifestations and complications of CKD. Presently some novel reagents to ameliorate anemia such as erythropoiesis-stimulating agents and erythropoietin receptor excitomotors, are in the process of clinical trials. In this paper we reviewed the novel remedies for correcting anemia and stimulating erythropoiesis; we also discussed the primary mechanisms and adverse effects of the treatment. The clinical treatment should be chosen according to the advantages and risks of each individual patients, so as to correct anemia, reduce risk of cardiovascular events, and eventually improve the life quality of patients with end-stage renal disease.

Anemia Management Practice in French Hemodialysis Centers.

Objective: Evaluate the hemoglobin (Hb) target values in hemodialysis (HD) patients treated with erythropoiesis-stimulating agents (ESA). Methods: Records of anemia parameters of HD patients treated during year 2012 in 5 French dialysis centers were retrospectively analyzed. Patients were stratified into “annual Hb categories” according to their monthly mean Hb: Low Hb (< 10 g/dL), Ideal Hb (from 10 to ≤ 12 g/dL), High Hb (> 12 g/dL) if they spent ≥ 75% of time in the respective category; otherwise patients were classified as Fluctuating Hb. Results: Out of 636 evaluable patients (mean age 66.6 [SD 14.9] years; male 59.4%), 91.4% received ESA treatment and 74.2% received intravenous iron. Most patients (68.9%) belonged to the Fluctuating Hb category (Ideal 18.7%; High 9.6%; Low 2.8%). Patients in the Fluctuating category experienced more frequently ESA dose changes, transfusions, hospitalizations and comorbidities compared with patients in other Hb categories. Multinomial logistic regression identified presence of at least one comorbidity (odds-ratio [OR]=7.6), hospitalization (OR=2.2), transfusion (OR=2.9), male gender (OR=0.6) and serum ferritin ≥500 vs. <200 μg/L (OR = 0.4) as predictors of Fluctuating vs. Ideal annual Hb category. Conclusions: Only 18.7% of patients had stable Hb levels within the target range according to French and international guidelines; most had fluctuating Hb levels and few patients had a consistently low annual Hb. These findings suggest that development and implementation of improved hematologic assessment and anemia treatment strategies are needed to minimize fluctuating Hb values in HD patients.

Situación actual de la anemia asociada a enfermedad renal en una muestra poblacional de pacientes con deterioro de la función renal, sin requerimientos de diálisis en la República Argentina - estudio APREDIA / Anemia associated renal functional impairment without dialysis requirements current situation in Argentina APREDIA study

Objetivo: El objetivo del trabajo APREDIA (Anemia prediálisis) fue detectar la prevalencia de la anemia en pacientes con Enfermedad Renal Crónica (ERC) etapa prediálisis y evaluar su manejo. Material y métodos: Para ello se realizó un relevamiento de datos de corte transversal, de pacientes con un filtrado glomerular (FG) ≤ 44,4 ml/min (Cockcroft Gault), en los que se excluyeron otras causas de anemia y/o evidencia de sangrado activo. La anemia se definió por hemoglobina (Hb) < 13 g/dl en hombres y 12 g/dl en mujeres. Se solicitaron datos acerca de: causa de ERC, laboratorios y tratamientos. Resultados: Se incluyeron datos de 611 pacientes (edad 71,4 ± 14 años). El 50% tenía 2 o más años de diagnóstico de ERC. El 71,7% presentaba un valor de Hb compatible con anemia (74% varones; 69% mujeres); el 64% y el 91% entre pacientes con FG entre 44,4 y 30 ml/min y ≤ 15 ml/min, respectivamente. El valor medio de Hb de toda la población fue de 11,4 g/dl, siendo más bajo a medida que disminuía el FG. Sólo el 35 % de los pacientes tenía un control de ferritina y ferremia, y sólo el 50,9% de los que tenían anemia recibía ferroterapia, la mayoría por vía oral. El 22,2% de los pacientes anémicos recibían agentes estimulantes de la eritropoyesis (AEE), el 31,2% y el 10,4% de los que tenían un FG < 30 ml/min y entre 30 y 44,4 ml/min, respectivamente. No hubo diferencias en los valores de Hb entre los que recibían AEE en los distintos estadíos, pero sí la hubo entre quienes no recibían AEE. Conclusiones: La anemia en el período predialítico de la ERC esta subdiagnosticada y subtratada, lo que explica el frecuente ingreso de los pacientes a terapia sustitutiva con signos de anemia severa, insuficientemente tratada.

The objective of APREDIA (Anemia predialysis) study was to detect the prevalence of anemia in patients with Chronic Kidney Disease (CKD) in predialysis stage and evaluate its management. For this purpose, a cross-sectional data survey of patients with a glomerular filtration rate (GF) ≤ 44.4 ml/min (Cockcroft Gault) was performed, in which other causes of anemia and/or evidence of active bleeding were excluded. Hemoglobin (Hb) < 13 g/dl for men and 12 g/dl for women defined anemia in our study. Data requested were: cause of CKD, laboratories, and treatments. Data of 611 patients (age 71.4 ± 14 years) were included. 50% of patients had been diagnosed with CKD 2 or more years ago. 71.7% had a Hb value compatible with anemia (74% males; 69% females); 64% of those who had GF between 44.4 and 30 ml/ min and 91% of those with GF ≤ 15 ml/min. The Hb medium value of the whole population was 11.4 g/dl, being lower as the GF decreased. Only 35% of the patients had a ferritin and iron serum measures, and only 50.9% of those who had anemia were receiving iron therapy, most of them orally. 22.2% of anemic patients received erythropoiesis-stimulating agents (ESAs), 31.2% of those who had a GF < 30 ml/min and 10.4% of those who had GF between 30 and 44.4 ml/ min. There were no differences in the levels of Hb among those who received ESAs in the different stages, but there was a difference among those who did not receive ESAs.According to our observation, we conclude that anemia in the predialysis stage of the CKD is underdiagnosed and undertreated. This explains why in patients who begin renal replacement therapy, signs of severe anemia are so common.

Oral Strip Technology: A review.

Over the recent past, many of the research groups are focusing their research on this technology. Amongst Oral drug delivery system Oral Strip Technology (OST) is gaining much attention. The advantages of OST are the administration to pediatric and geriatric patient population where the difficulty of swallowing larger oral dosage forms is eliminated. This technology has been used for local action, rapid release products and for buccoadhesive systems that are retained in the oral cavity to release drug in controlled fashion. OST offers an alternate platform for molecules that undergo first pass metabolism and for delivery of peptides. An ideal OST should have the following properties: high stability, transportability, ease of handling and administration, no special packaging material and/or processing requirements, no water necessary for application, and a pleasant taste. All these requirement are fulfilled by the oral films. The OST is a good tool for product life cycle management for increasing the patent life of existing molecules or products. Compared to some of the complicated and expensive process (like lyophilization) used to manufacture ODTs(Orally Disintegrating Tablets), the OST is relatively easy to fabricate,thus reducing the overall cost of the therapy. One of the reasons is that the buccal mucosa is less permeable and is thus not able to elicit a rapid onset of absorption and hence better suited for formulations that are intended for sustained release action. Further, the buccal mucosa being relatively immobile mucosa and readily accessible, it makes it more advantageous for retentive systems used for oral trans mucosal drug delivery. The primary disadvantage associated with buccal delivery route is the low flux that in turn results in low drug bioavailability. To overcome this hurdle, various buccal penetration enhancers have been studied which improve the absorption pattern of the molecules. The article shows OST encompassing materials used in OST, method of preparation, evaluation, applications, commercial technologies and future Business prospects of this technology.

Cardiovascular effects of hemoglobin response in patients receiving epoetin alfa and oral iron in heart failure with a preserved ejection fraction / 老年心脏病学杂志（英文版）

Background Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with heart failure with a preserved ejection fraction (HFPEF) and anemia randomized to treatment with epoetin alfa (erythro-poiesis-stimulating agents, ESA) vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular (LV) structure, functional capacity, or quality of life (QOL). However, several patients randomized to the treatment arm were non-responders with a subop-timal increase in hemoglobin. All patients in the trial also received oral ferrous gluconate, which could have contributed to increases in he-moglobin observed in those receiving placebo. Accordingly, we performed an analysis separating patients into responders vs. non-responders in order to determine if measured improvement in anemia would have any effect on clinical endpoints. Methods A total of 56 patients (age 77 ± 11 years, 68%female) were recruited who had anemia defined as a hemoglobin of≤12 g/dL (average, 10.4 ± 1 g/dL) with HFPEF defined as having NHANES-CHF (National Health And Nutrition Examination Survey:Congestive Heart Failure) criteria score of≥3 and an ejection fraction of>40%(average EF=63%±15%). Patients were randomly allocated to receive either ESA and ferrous gluconate or ferrous gluconate only. In this analysis, a responder was defined as a patient with an increase of 1 g/dL in the first 4 weeks of the trial. Re-sults Nineteen subjects were classified as responders compared to 33 non-responders. While the average hemoglobin increased signifi-cantly at the end of 6 months for responders (1.8 ± 0.3 vs. 0.8 ± 0.2 g/dL, P = 0.004), 50% of the subjects assigned to ESA were non-responders. Left ventricular function including ejection fraction (P=0.32) and end diastolic volume (P=0.59) was unchanged in res-ponders compared to non-responders. Responders also showed no significant improvements in New York Heart Association (NYHA) class, Six Minute Walk Test (6 MWT) and peak VO2. Though QOL improved significantly within each group, there was no difference between the two. Conclusions A significant hemoglobin response to anemia treatment with ESA and oral iron does not lead to differences in LV re-modeling, functional status, or QOL. Additionally, a significant percent of older adults with HFPEF and anemia do not respond to ESA ther-apy. Given the results of this small trial, it appears as though using objective improvements in anemia as a marker in older adult subjects with HFPEF does not have significant clinical utility.

Recent Advances in the Drug Therapy of Osteoporosis / 영남의대학술지

Osteoporosis is one of the most important public health problems facing the aging population. Drug therapy for osteoporosis can be divided operationally into two main categories: drugs that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Antiresorptive agents such as estrogens, calcitonin, and bisphosphonates are most effective in the prevention of osteoporosis. Formation-stimulating agents such as sodium fluoride or monofluorophosphate, parathyroid hormone fragments, and anabolic steroids are of potential value in the treatment of established osteoporosis, where bone mass s already low and benefit from antiresorptive drug is likelyto be small. Recently, raloxifene, a selective estrogen receptor modulator, has become available in various countries for clinical use in the treatment of involutional osteoporsis . This paper will review the use of these drugs in postmenopausal woman.