losartan-potassium and Protein-Energy-Malnutrition

Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.

Topics: Acute-Phase Reaction; Anemia; Chronic Disease; Erythropoietin; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Protein-Energy Malnutrition; Quality of Life; Recombinant Proteins; Renal Dialysis; Syndrome; Wasting Syndrome

Since many end stage renal disease (ESRD) patients experi inflammation, malnutrition, and anemia, the interplay of these processes should be considered in the approach to patients treated with erythropoietin (EPO). This article reviews the interrelationship between these factors. The systemic inflammatory response caused by exposure to inflammatory stimuli results in anorexia and metabolic disturbances leading to protein calorie malnut tion as well as sequestration of iron and hyporesponsiveness to EPO. The implications of these effects and possible strategies to optimize anemia management in the presence of these conditions are discussed.

Topics: Anemia, Iron-Deficiency; Clinical Protocols; Drug Monitoring; Erythropoietin; Ferritins; Hematinics; Humans; Iron; Iron-Binding Proteins; Iron-Dextran Complex; Kidney Failure, Chronic; Nutritional Status; Nutritional Support; Protein-Energy Malnutrition; Risk Factors; Systemic Inflammatory Response Syndrome; Treatment Outcome

Topics: Adolescent; Adult; Anemia; Anemia, Hypochromic; Anemia, Megaloblastic; Animals; Child; Child, Preschool; Dapsone; Drug Combinations; Erythropoietin; Female; Hookworm Infections; Humans; Infant; Iron-Dextran Complex; Leishmaniasis, Visceral; Macaca mulatta; Malaria; Male; Mice; Middle Aged; Protein-Energy Malnutrition; Pyrimethamine; Schistosomiasis; Socioeconomic Factors; Tropical Medicine; Trypanosomiasis, African

Dialysis patients with a high body mass index are less likely to experience severe anemia. Leptin, a hormone secreted by adipocytes, may have a role in protecting against renal anemia. The aim of the present study is to determine the effect of an increase in serum leptin levels by increasing energy intake on recombinant human erythropoietin (rHuEPO) response in long-term hemodialysis (HD) patients.. We enrolled 65 long-term HD patients to explore the association between leptin level and rHuEPO response by classifying them as either high- or low-leptin individuals (phase 1). Thereafter, 39 patients with malnutrition by means of Subjective Global Assessment were randomly assigned to high-energy and high-protein (an extra 475 kcal and 16.6 g of protein daily; group A; n = 12) or standard-energy, but high-protein (an extra 67.2 kcal and 16.8 g of protein daily; group B; n = 27), supplementation for 12 weeks. Serial serum leptin levels, nutritional measures, and hematologic parameters were obtained. Age- and sex-matched well-nourished patients (group C; n = 16) not administered extra nutritional supplementation served as control subjects (phase 2).. In phase 1, a significantly lower erythropoietin dose, greater hematocrit, and better nutritional measures were observed in the high-leptin group (P < 0.001). In phase 2, there was a significant increase in body fat mass (P = 0.001) and median serum leptin levels (P < 0.001) in response to 12 weeks of high-energy supplementation in group A, accompanied by markedly improved erythropoiesis (P < 0.05) compared with groups B and C.. Hyperleptinemia reflects better nutritional status and rHuEPO response in long-term HD patients. Increasing energy intake improves erythropoiesis, which may be mediated in part by an increase in serum leptin levels.

Topics: Adipose Tissue; Aged; Anemia; Body Composition; Cross-Sectional Studies; Dietary Proteins; Dietary Supplements; Drug Resistance; Energy Intake; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis; Treatment Outcome

It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO).. Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the "Malnutrition Inflammation Score" (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant.. Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329-0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS (p < 0.05).. PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

Topics: Adult; Aged; Anemia; Body Composition; Creatinine; Drug Resistance; Electric Impedance; Erythropoietin; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hematocrit; Hemoglobin A; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Status; Probability; Protein-Energy Malnutrition; Renal Dialysis; Retrospective Studies; Risk; Sex Factors; Statistics, Nonparametric; Time Factors; Young Adult

Protein-energy malnutrition is a syndrome in which anaemia together with multivitamin and mineral deficiency may be present. The pathophysiological mechanisms involved have not, however, yet been completely elucidated. The aim of the present study was to evaluate the pathophysiological processes that occur in this anaemia in animals that were submitted to protein-energy malnutrition, in particular with respect to Fe concentration and the proliferative activity of haemopoietic cells. For this, histological, histochemical, cell culture and immunophenotyping techniques were used. Two-month-old male Swiss mice were submitted to protein-energy malnutrition with a low-protein diet (20 g/kg) compared with control diet (400 g/kg). When the experimental group had attained a 20 % loss of their original body weight, the animals from both groups received, intravenously, 20 IU erythropoietin every other day for 14 d. Malnourished animals showed a decrease in red blood cells, Hb concentration and reticulocytopenia, as well as severe bone marrow and splenic atrophy. The results for serum Fe, total Fe-binding capacity, transferrin and erythropoietin in malnourished animals were no different from those of the control animals. Fe reserves in the spleen, liver and bone marrow were found to be greater in the malnourished animals. The mixed colony-forming unit assays revealed a smaller production of granulocyte-macrophage colony-forming units, erythroid burst-forming units, erythroid colony-forming units and CD45, CD117, CD119 and CD71 expression in the bone marrow and spleen cells of malnourished animals. These findings suggest that, in this protein-energy malnutrition model, anaemia is not caused by Fe deficiency or erythropoietin deficiency, but is a result of ineffective erythropoiesis.

Topics: Anemia; Animals; Blood Proteins; Body Weight; Bone Marrow Cells; Colony-Forming Units Assay; Dietary Proteins; Disease Models, Animal; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Flow Cytometry; Immunophenotyping; Iron; Male; Mice; Protein-Energy Malnutrition; Spleen; Transferrin

Possible interactions between inflammatory and nutritional markers and their impact on recombinant human erythropoietin (rHuEPO) hyporesponsiveness are not well understood. We investigated the role of nutritional status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without evidence of inflammation. This cross-sectional study included 88 MHD patients. The associations between required rHuEPO dose and malnutrition-inflammation score (MIS) and several laboratory values known to be related to nutrition and/or inflammation were analyzed. Anthropometric measures including body mass index, triceps skinfold thickness, and midarm circumferences were also measured. Twenty-three patients with serum C-reactive protein levels >10 mg/L were excluded from the analysis. The remaining 65 patients (male/female, 41/24; age 49.1+/-11.4 years; dialysis duration 99.7+/-63.0 months) were studied. These patients had moderate malnutrition and the average MIS was 7.4 (range 3-17). The average weekly dose of administered rHuEPO was 69.1+/-63.1 U/kg. Malnutrition-inflammation score had a positive correlation with the serum concentration of tumor necrosis factor-alpha, whereas it had a negative correlation with anthropometric measures, total iron-binding capacity, prealbumin, phosphorus, creatinine, and triglyceride. According to Pearson's correlation analysis, significant relationships of increased MIS with increased required rHuEPO dose and rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=-0.326; p=0.017, r=-0.306, respectively). Recombinant human erythropoietin dose requirement is correlated with MIS and adverse nutritional status in MHD patients without evidence of inflammation. Further research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.

Topics: Adult; Anthropometry; Erythropoietin; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Nutrition Assessment; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis

Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Topics: Anemia; Chronic Disease; Darbepoetin alfa; Drug Resistance; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Malnutrition; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis

We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up.. A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values.. Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses.. In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Topics: Aged; Bicarbonates; Body Composition; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cholesterol; Comorbidity; Creatinine; Diabetic Nephropathies; Erythropoietin; Female; Follow-Up Studies; Humans; Infections; Kidney Failure, Chronic; Life Tables; Male; Membranes, Artificial; Middle Aged; Neoplasms; Permeability; Prealbumin; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Survival Analysis; Time Factors; Urea

Although a known cardiovascular risk factor, anemia in the renal transplant recipients has only recently been receiving an increasing attention.. In a cross-sectional study, data was obtained from 959 patients followed at a single outpatient transplant clinic. Based on the guideline of the American Society of Transplantation, anemia was defined as hemoglobin (Hb) < or =130 g/L in males and < or =120 g/L in females.. About one-third (34%) of the patients were anemic. The prevalence of anemia was comparable in males and females. Serum Hb concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (abbreviated modification of diet in renal disease formula) (r = 0.266, p < 0.001), serum transferrin (r = 0.268, p < 0.001) and serum albumin (r = 0.196, p < 0.001). None of the immunosuppressive medications or the use of angiotensin converting enzyme inhibitors was associated with a higher likelihood of anemia. In multivariate analysis the eGFR, serum albumin and serum transferrin, potential markers of nutritional status and/or chronic inflammation, and also iron deficiency were independently and significantly associated with anemia. Erythropoietin was administered only to 63 (19%) anemic patients.. Post-transplant anemia is a prevalent and under-treated condition. Based on our results we suggest that, besides other factors, protein/energy malnutrition and/or chronic inflammation may be independently associated with anemia. Further studies are needed to determine whether the presence of anemia and its treatment will have an impact on long-term outcomes of this population.

Topics: Adult; Anemia, Iron-Deficiency; Angiotensin-Converting Enzyme Inhibitors; Comorbidity; Cross-Sectional Studies; Erythropoietin; Female; Humans; Inflammation; Kidney Transplantation; Male; Middle Aged; Multivariate Analysis; Protein-Energy Malnutrition; Recombinant Proteins; Transferrin

The anemia of chronic disease is mediated by the cytokines that modulate the immune response, such as tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN), and is associated with a blunted serum erythropoietin (sEPO) response to anemia. Previous reports suggest that patients with liver disease (LD) also exhibit a blunted sEPO response to anemia, and that patients with alcoholic LD had altered cytokines, including elevated TNF levels. To investigate the pathogenesis of anemia in alcoholic LD, sEPO, TNF, and gamma-IFN levels were determined in patients who had participated in a Department of Veterans Affairs Cooperative study of alcoholic LD.. sEPO, serum TNF-alpha, and serum gamma-IFN levels were evaluated in 40 patients with severe biopsy-proven alcoholic LD whose serum had been stored during the Department of Veterans Affairs Cooperative Study 275, and in 18 patients with iron deficiency (controls).. Mean hemoglobin (Hgb) was 11.2 +/- 0.3 g/dl for LD patients versus 11.4 +/- 0.4 g/dl for controls (p = 0.84). sEPO levels measured by ELISA were 29.6 +/- 4.1 units/liter in LD patients versus 25.4 +/- 5.4 units/liter in controls (p = 0.64). In both sets of patients, sEPO and Hgb were inversely related; the slopes of the two regression lines did not differ significantly (p = 0.92). TNF was detected in 3 of 40 LD patients and in 0 of 18 iron-deficient patients. Detection of TNF did not correlate with sEPO or Hgb, but did correlate strongly with severe caloric malnutrition (marasmus) and mortality at 6 months (p = 0.049 and 0.04, respectively). gamma-IFN was not detected.. These findings indicate that the sEPO response is preserved in patients with severe alcoholic LD, and suggest that anemia in LD arises from different mechanisms than does the anemia of chronic disease. TNF production in severe alcoholic LD is strongly correlated with caloric malnutrition and mortality.

Topics: Anemia; Anemia, Iron-Deficiency; Combined Modality Therapy; Cytokines; Erythropoietin; Hemoglobinometry; Humans; Liver Diseases, Alcoholic; Nutritional Status; Protein-Energy Malnutrition; Reference Values; Tumor Necrosis Factor-alpha

Topics: Animals; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematocrit; Insulin-Like Growth Factor I; Iron; Protein-Energy Malnutrition; Rats; Rats, Wistar

Immunoreactive erythropoietin was estimated in the sera of 23 Nigerian children with protein-energy malnutrition (PEM) and 14 healthy Nigerian children of similar age attending a well baby clinic. The geometric mean estimate for this parameter was 262 mIU/ml (observed range 39-1340 mIU/ml; 95% confidence range 25-1738 mIU/ml) in the children with PEM and 80 mIU/ml (observed range 43-257 mIU/ml; 95% confidence range 27-241 mIU/ml) in the health children. Erythropoietin levels were above the 95% confidence range for the healthy children in 14 of the cases of PEM. There was a statistically significant inverse correlation between the haemoglobin levels of the children with PEM and the logarithm of immunoreactive serum erythropoietin estimates (r = -0.73; P less than 0.001). By contrast, statistically significant correlations were not found between the logarithm of erythropoietin estimates and either the percentage of erythroblasts in the marrow, the M/E ratio or the logarithm of the absolute blood reticulocyte count. These data suggest that there is no abnormality of erythropoietin production in PEM and that the anaemia seen in this condition results from an impairment of erythropoiesis. A stepwise multiple regression analysis revealed a positive correlation between the logarithm of the erythropoietin level and the logarithm of the concentration of circulating neutrophil metamyelocytes plus myelocytes and we speculate on the aetiology of this finding.

Topics: Child, Preschool; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Infant; Leukocyte Count; Male; Neutrophils; Protein-Energy Malnutrition

Studies of red cell metabolism, erythropoeitin concentration, iron and folate status were made in 48 children with protein-energy malnutrition in Johannesburg (altitude 1800 m). Biochemical evidence of iron deficiency was presented in 26% cases on admission and developed in 90% during recovery. Biochemical evidence of folate deficiency was present in 14% of cases on admission and resolved on dietary therapy alone. Serum erythropoeitin was increased on admission and remained elevated during recovery. There was no relationship between serum erythropoeitin and Hb concentrations. Key enzymes in the red cell glycolytic and hexose monophosphate pathways and red cell membrane showed increased activity. Red cell adenosine triphosphate concentration was increased and unstable. Red cell potassium was decreased and, in the fatal cases, red cell sodium was increased. The possible significance and practical implications of these findings are discussed.

Topics: Adenosine Triphosphatases; Anemia, Hypochromic; Child, Preschool; Erythrocytes; Erythropoietin; Folic Acid; Hemolysis; Humans; Infant; Iron; Potassium; Protein-Energy Malnutrition; Sodium; South Africa

The erythropoietin (ESF) content of plasma and urine has been studied in children with protein-energy-malnutrition (PEM) living in the Kivu province at an altitude of 1467--2000 m. On admission, packed cell volume (PCV) was moderately reduced; after 2 months of refeeding PCV had increased but was still lower than in the controls. Plasma ESF was increased on admission and in patients refed for 2 months. The expected positive correlation between serum and urine ESF levels was found after refeeding but not on admission; the last finding could not be explained by the presence of erythropoiesis inhibiting factor(s) in the urine. In spite of the normal 2,3-DPG and P50 previously described in PEM in Kivu, the anaemia associated with this disease is not merely an adaptation to lowered oxygen consumption and there must be some disturbances in the responsiveness of bone marrow to ESF. The high ESF values observed after 2 months of refeeding confirm that the restoration of the red cell volume proceeds slowly.

Topics: Adolescent; Child; Child, Preschool; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Infant; Male; Protein-Energy Malnutrition