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Effect of Oral Branched-Chain Amino Acids on Serum Albumin Concentration in Heart Failure Patients with Hypoalbuminemia: Results of a Preliminary Study.
Uchino, Y, Watanabe, M, Takata, M, Amiya, E, Tsushima, K, Adachi, T, Hiroi, Y, Funazaki, T, Komuro, I
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(4):327-332
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BACKGROUND We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT®) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy. The primary endpoints were changes from baseline in serum albumin and cardiothoracic ratio (CTR). Sixteen patients completed the study. The mean (± standard deviation) period of BCAA supplementation was 18.4 ± 8.4 days. Serum albumin significantly increased in the BCAA group [mean difference vs baseline, 0.44 g/dL; 95% confidence interval (CI) 0.13-0.76; P = 0.014] and did not change in controls (0.18 g/dL; 95% CI - 0.05 to 0.40; P = 0.108). CTR significantly decreased in the BCAA group (- 2.3%; 95% CI - 3.8 to - 0.8; P = 0.014) and did not change in controls (- 1.0%; 95% CI - 2.3 to 0.3; P = 0.111). CONCLUSION In-hospital HF patients with hypoalbuminemia supplemented with BCAAs showed increased serum albumin and decreased CTR. Clinical trial registration number UMIN000004488 [ http://www.umin.ac.jp/ctr/index.htm ].
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The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin.
Ghashut, RA, Talwar, D, Kinsella, J, Duncan, A, McMillan, DC
PloS one. 2014;(3):e92614
Abstract
BACKGROUND Plasma 25-hydroxyvitamin D (25(OH) D) deficiencies are associated with several diseases. The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower 25(OH)D. Other aspects of the systemic inflammatory response may be important in determining plasma 25 (OH)D concentrations. AIM: To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts. METHODS 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was <10%. RESULT In the large cohort, plasma 25 (OH) D was significantly associated with CRP (r(s) = -0.113, p<0.001) and albumin (rs = 0.192, p<0.001). 3711 patients had CRP concentrations ≤ 10 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p<0.001). This decrease was significant when albumin concentrations were reduced between 25-34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 1271 patients had CRP concentrations between 11-80 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p<0.001). This decrease was significant when albumin concentration were 25-34 g/L (p<0.001) and when albumin <25 g/L (p<0.001). 345 patients had CRP concentrations >80 mg/L; with decreasing albumin concentrations ≥ 35, 25-34 and <25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness. CONCLUSION Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.
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Association of serum albumin concentration with mortality, morbidity, CD4 T-cell reconstitution among tanzanians initiating antiretroviral therapy.
Sudfeld, CR, Isanaka, S, Aboud, S, Mugusi, FM, Wang, M, Chalamilla, GE, Fawzi, WW
The Journal of infectious diseases. 2013;(9):1370-8
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BACKGROUND Prospective studies of serum albumin concentration measurement as a low-cost predictor of human immunodeficiency virus (HIV) disease progression are needed for individuals initiating antiretroviral therapy (ART) in resource-limited settings. METHODS Serum albumin concentration was measured at ART initiation for 2145 adults in Tanzania who were enrolled in a trial examining the effect of multivitamins on HIV disease progression. Participants were prospectively followed for mortality, morbidity, and anthropometric outcomes at monthly visits (median follow-up duration, 21.2 months). Proportional hazard models were used to analyze mortality, morbidity, and nutritional outcomes, while generalized estimating equations were used to analyze CD4(+) T-cell counts. RESULTS Individuals with hypoalbuminemia (defined as a serum albumin concentration of <35 g/L) at ART initiation had a hazard of death that was 4.52 times (95% confidence interval, 3.37-6.07; P < .001) that of individuals with serum albumin concentrations of ≥ 35 g/L, after multivariate adjustment. Hypoalbuminemia was also independently associated with the incidence of pulmonary tuberculosis (P < .001), severe anemia (P < .001), wasting (P = .002), and >10% weight loss (P = .012). Secondary analyses suggested that serum albumin concentrations of <38 g/L were associated with increased mortality and incident pulmonary tuberculosis. There was no association between serum albumin concentration and changes in CD4(+) T-cell counts (P = .121). CONCLUSIONS Serum albumin concentrations can identify adults initiating ART who are at high risk for mortality and selected morbidities. Future research is needed to identify and manage conditions that reduce the serum albumin concentration.
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Influence of ezetimibe monotherapy on ischemia-modified albumin levels in hypercholesterolemic patients.
Kotani, K, Caccavello, R, Sakane, N, Miyamoto, M, Gugliucci, A
Pharmacological reports : PR. 2011;(5):1248-51
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Ischemia-modified albumin (IMA) is considered to be a novel biochemical marker for ischemic and atherosclerotic conditions. This study aimed to investigate the influence of ezetimibe monotherapy on circulating IMA levels in hypercholesterolemic patients. A total of 31 patients (mean age 65.7 years) received 10 mg of ezetimibe daily during a 12-week treatment period. The levels of low-density lipoprotein cholesterol and IMA were significantly reduced after ezetimibe treatment. The adjusted regression analyses revealed that the changes in the IMA levels were not significantly correlated with those of the other atherosclerotic risk markers, such as body mass index, blood pressure, glucose and lipid panels. The significant reduction of the IMA levels following ezetimibe treatment, which was independent of the reduction of low-density lipoprotein cholesterol levels, suggests that ezetimibe may improve the oxidative stress burden in hypercholesterolemic patients.
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Serum albumin is strongly associated with erythropoietin sensitivity in hemodialysis patients.
Agarwal, R, Davis, JL, Smith, L
Clinical journal of the American Society of Nephrology : CJASN. 2008;(1):98-104
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BACKGROUND AND OBJECTIVES In hemodialysis patients, the hematological response to erythropoietin (epo) is variable and clinical factors that explain this variability are incompletely understood. We tested the hypothesis that the variability in hemoglobin (Hgb) response (epo sensitivity) is determined by key nutritional, inflammation, and oxidative stress markers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Eighty-two consecutive patients on hemodialysis had 3 consecutive monthly predialysis evaluations of Hgb, total white blood cell (WBC) count, serum albumin, malondialdehyde (MDA), and monocyte chemoattractant protein-1 (MCP1). We analyzed the time course of Hgb in relationship to serum albumin, WBC, MDA, MCP1, epo and iron administration, and tests of iron sufficiency in a linear growth curve model. RESULTS Subjects with higher Hgb had a fall in Hgb and vice versa, regressing to a mean Hgb (SD) of 11.8 g/dl (1.8 g/dl). Whereas the average slope of Hgb was flat, the SD of slopes was 0.63 g/dl, which explained 39% of the variance in Hgb. Nonuse of epo was associated with a mean Hgb change of -0.18 g/dl (95% confidence interval [CI] -0.26 to -0.10) per 10,000 IU epo/mo (P < 0.05). Epo use was associated with steeper rate of change at 0.04 g/dl per mo per 10,000 IU (95% CI 0.01 to 0.07) (P < 0.01). Hgb at baseline was 0.73 g/dl higher for each 1-g/dl increase in albumin, and the rate of change increased by 0.49 g/dl per mo for each 1-g/dl increase in albumin concentration. WBC, MDA, or MCP1 had no role in predicting the baseline Hgb or its change over time. CONCLUSIONS Serum albumin concentration is an important predictor of both baseline Hgb and epo sensitivity in chronic hemodialysis patients. Factors that improve serum albumin may also improve Hgb in hemodialysis patients.
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Significant association of serum albumin with severity of retinopathy and neuropathy, in addition to that of nephropathy, in Japanese type 2 diabetic patients.
Iwasaki, T, Togashi, Y, Terauchi, Y
Endocrine journal. 2008;(2):311-6
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OBJECTIVE The aim of this study was to determine the association between serum albumin and the severity of microvascular complications and presence of coronary artery disease in type 2 diabetic patients. PATIENTS AND METHODS The presence of diabetic complications was assessed in a total of 130 Japanese patients with type 2 diabetes mellitus. Retinopathy was classified as absent, simple or proliferative diabetic retinopathy. Neuropathy was considered to be present when the patient showed absence of Achilles tendon reflex, and also evaluated by measuring the median motor nerve conduction velocity (MNCV) in the nerve conduction study. RESULTS In relation to retinopathy, there were 83 patients with no retinopathy (absent), 26 with simple retinopathy and 21 with proliferative retinopathy. There was a significant difference in the serum albumin level between the "absent" group and the other two groups. In relation to nephropathy, there were 68 patients with no evidence of nephropathy, 49 with microalbuminuria and 13 with proteinuria. The results of logistic regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to proliferative retinopathy and proteinuria. In relation to neuropathy, serum albumin was found to be significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL. The results of multiple regression analysis with adjustment for three variables (age, gender, serum CRP) revealed that serum albumin was independently related to MNCV and MFWL. CONCLUSIONS Serum albumin was significantly associated with the severity of retinopathy and neuropathy.
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On the nature of proteinuria with acute renal injury in patients with chronic kidney disease.
Agarwal, R
American journal of physiology. Renal physiology. 2005;(2):F265-71
Abstract
Albuminuria is an excellent marker of cardiovascular and renal prognosis. Commercially available tests of immunodetectable albumin in the urine may not identify posttranslationally modified albumin that makes it undetectable to antibodies. Also, it is unclear whether albumin is degraded to smaller fragments, such as through proteolysis, in the course of acute renal injury. In 20 men with chronic kidney disease, we measured excretion rates of urinary protein (pyragallol red), immundetectable urinary albumin (immunoturbidimetry), and urinary total intact albumin (HPLC) after a single dose of 100 mg intravenous iron sucrose administered over 5 min. Fragmentation of urinary albumin and carbonylation of urinary proteins were assessed by immunoblotting. Results showed that iron infusion increased carbonylation of plasma and urinary proteins in a time-dependent manner. A transient increase in urinary excretion rates of total protein, immunodetectable urinary albumin, and total intact albumin was seen. Fragmentation and loss of immunoreactivity of albumin paralleled the changes in total protein excretion. In conclusion, fragmentation, loss of immunoreactivity, and oxidation of albumin in a time-dependent manner may underestimate the extent of injury with the immunoreactive microalbumin assay. Measurement of total intact albumin may better quantify acute renal injury.
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C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.
Menon, V, Greene, T, Wang, X, Pereira, AA, Marcovina, SM, Beck, GJ, Kusek, JW, Collins, AJ, Levey, AS, Sarnak, MJ
Kidney international. 2005;(2):766-72
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BACKGROUND High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. METHODS The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. RESULTS Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. CONCLUSION Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.
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Randomized double-blind trial of oral essential amino acids for dialysis-associated hypoalbuminemia.
Eustace, JA, Coresh, J, Kutchey, C, Te, PL, Gimenez, LF, Scheel, PJ, Walser, M
Kidney international. 2000;(6):2527-38
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BACKGROUND Hypoalbuminemia is associated with substantial morbidity and mortality in dialysis patients. METHODS Subjects with a mean three-month prestudy serum albumin of 3.8 g/dL or less and who demonstrated ≥90% compliance during a two-week run-in period were randomized to 3.6 g of essential amino acids (EAAs) or placebo three times daily with meals for three months. Randomization was stratified by dialysis modality and by severity of the hypoalbuminemia. The primary study outcome was change in the average of three monthly serum albumin measurements between baseline and follow-up. RESULTS Fifty-two patients were randomized; 47 patients (29 hemodialysis and 18 peritoneal dialysis) met the predetermined primary analysis criteria. The mean compliance rates averaged 75, 70, and 50% at months 1, 2, and 3, respectively, and were similar for EAAs and placebo. Serum albumin in the hemodialysis patients, EAA versus placebo, improved [(mean +/- SE) 0.22 +/- 0.09 g/dL, P = 0.02]. Changes in peritoneal dialysis patients were not significant (0.01 +/- 0.15 g/dL), but approached significance for the total study group (0.14 +/- 0.08 g/dL, P = 0.08). Patients in the very low albumin strata (<3.5 g/dL) improved more than those in the low albumin strata (3.5 to 3.8 g/dL, P < 0.01). There was a significant correlation (r = 0.83, P = 0.001) within the hemodialysis EAA group between the baseline C-reactive protein level and improvement in serum albumin. Improvements were also seen in grip strength and SF-12 mental health score, but not in serum amino acid levels, SF-12 physical health score, or anthropometric measurements. CONCLUSIONS Oral EAAs induce a significant improvement in the serum albumin concentration in hemodialysis but not peritoneal dialysis subjects. Further study of their long-term effects on morbidity and mortality is warranted.