Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients

BACKGROUND: Serum albumin concentration is a balance among its synthesis rate, fractional catabolic rate (FCR), distribution, dilution in the plasma pool and external loss. The physiologic bases for establishing the level of serum albumin in hemodialysis patients have not been defined despite the association of hypoalbuminemia with excess mortality. Albumin concentration is associated with the levels of several acute phase proteins (APPs), C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), or ceruloplasmin, and with nutritional markers, such as normalized protein catabolic rate (nPCR). METHODS: To establish the relationship among parameters that regulate albumin levels and markers of nutrition and inflammation, we injected [125I]-albumin, into 64 hemodialysis patients enrolled in the HEMO study to measure albumin distribution, synthesis and FCR. These variables were related to the levels of acute phase proteins (APPs), nPCR, body mass index (BMI), external albumin loss as well as demographic variables. Albumin distribution, synthesis and FCR were calculated from kinetic modeling, as was the initial plasma volume (PV). Serum albumin, transferrin, CRP, ceruloplasmin and alpha1 AG were measured weekly. Dialysate was collected during one dialysis each week to measure albumin loss. Results were analyzed by multiple linear regression. RESULTS: Albumin concentration correlated with its synthesis rate and FCR, but not with PV or its distribution between the vascular and extravascular pools. Albumin concentration also correlated with nPCR and alpha1 AG. However, albumin synthesis was directly related most strongly to PV and BMI (or nPCR), but not to levels of APPs. By contrast, albumin FCR correlated positively with both alpha1 AG and ceruloplasmin. CONCLUSION: Albumin concentration in dialysis patients changes with inflammation and nutritional status through their effects on albumin catabolism and synthesis, respectively. Within the range of albumin levels in these patients, nutritional variables primarily affected albumin synthesis while inflammation caused hypoalbuminemia by increasing albumin FCR. Albumin synthesis also increased in proportion to PV. The result of this is that PV expansion does not contribute to hypoalbuminemia.     

Impact of albumin synthesis rate and the acute phase response in the dual regulation of fibrinogen levels in hemodialysis patients

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease. It also is an acute phase protein (APP) and its plasma concentration increases with inflammation. Fibrinogen synthesis correlates with albumin synthesis in nephrotic patients and in patients with an expanded plasma volume even when serum albumin is normal and there is no inflammatory disease. The relationships among albumin synthesis, the acute phase response and plasma fibrinogen levels in hemodialysis patients are unknown. METHODS: In 74 hemodialysis patients, albumin synthesis, plasma volume (PV) and acute phase proteins (APPs) C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1 AG), ceruloplasmin (Cer), and interleukin 6 (IL-6) were measured in serum and fibrinogen in plasma, and the results analyzed by multiple regression analysis. CRP, IL-6, alpha1 AG, Cer and fibrinogen were measured monthly, which enabled us to determine whether changes in these APPs correlated with the levels of and variability in plasma fibrinogen over time using a longitudinal modeling approach. Length of follow-up for the 74 patients ranged from 3.25 to 67.5 months. RESULTS: Baseline fibrinogen (548.6 +/- 106. 4 mg/dL) was significantly greater than levels reported for normal adults and correlated positively with albumin synthesis (P < 0.001), age (P < 0.001) and log CRP (P = 0.002) and negatively with PV (P < 0.001). Longitudinally, fibrinogen varied positively with long-lived APPs, Cer and alpha1 AG, as well as the short-lived APP, CRP. CONCLUSION: Plasma fibrinogen concentration is high in HD patients and directly correlates with increased albumin synthesis rates and the serum levels of APPs. Fibrinogen levels also correlate negatively with PV. Fibrinogen levels vary over time in synchrony with levels of other long-lived APPs, supporting the hypothesis that fibrinogen is regulated in part as a component of the acute phase response and in part by factors that increase albumin synthesis.     

Levels of alpha1 acid glycoprotein and ceruloplasmin predict future albumin levels in hemodialysis patients.

BACKGROUND: Serum albumin concentration predicts mortality in hemodialysis (HD) patients. While serum albumin concentration correlates with serum concentration of C-reactive protein (CRP) and is dependent upon CRP in multiple regression models in cross sectional studies, CRP does not predict future albumin levels, possibly because CRP changes rapidly, yielding large month-to-month variability in CRP. If inflammation causes rather than is simply associated with hypoalbuminemia, then changes in the levels of acute phase proteins should precede changes in serum albumin concentration. METHODS: The levels of long-lived positive and negative acute-phase proteins (APPs) (C-reactive protein, ceruloplasmin, alpha1 acid glycoprotein, transferrin and albumin) were measured longitudinally in 64 HD patients and a regression model was constructed to predict future albumin levels. Normalized protein catabolic rate (nPCR) was measured monthly. The number of repeated measurements ranged from 9 to 39 in each patient (median 22 and a mean of 23 measurements). To construct a model that would predict serum albumin concentration at any time j, values of all longitudinally measured APPs, positive and negative at any time j - 1, approximately 30 days prior to time j, were used. Other demographic factors (such as, race, access type, and cause of renal failure) also were incorporated into the model. RESULTS: The model with the best fit for predicting serum albumin at time j included albumin, ceruloplasmin, and alpha1 acid glycoprotein measured at time j - 1. The only demographic variable with subsequent predictive value was diabetes. CONCLUSIONS: The finding that changes in the concentration of the long lived APPs measured one month earlier are associated with predictable changes in the future concentration of serum albumin suggest that changes in inflammation are likely to be causal in determining serum albumin concentration in hemodialysis patients.     

Factors that affect albumin concentration in dialysis patients and their relationship to vascular disease

INTRODUCTION: Hypoalbuminemia is a powerful risk factor for cardiovascular mortality in hemodialysis patients (HD). Inflammation causes a decrease in albumin synthesis and an increase in albumin fractional catabolic rate, providing two mechanisms for hypoalbuminemia. The inflammatory response alters the endothelium and plasma protein composition in ways that favor vascular injury. Plasma volume is expanded in HD patients, providing another mechanism for hypoalbuminemia. Fibrinogen levels are an independent risk factor for cardiovascular disease (CVD) in HD patients, and fibrinogen levels are increased in HD patients. Plasma volume expansion is also an independent risk factor for CVD. METHODS: Albumin synthesis was measured in 74 HD patients as the disappearance of [125I] human albumin over six weeks. Fibrinogen was measured in plasma. Plasma fibrinogen mass was the product of fibrinogen concentration and plasma volume. RESULTS: Albumin synthesis correlated positively with plasma volume (P < 0.001). Fibrinogen concentration and plasma fibrinogen mass both correlated positively with albumin synthesis (P < 0.001). CONCLUSION: Albumin levels are reduced as part of the acute-phase response in HD. Plasma volume expansion also tends to decrease albumin concentration, but elicits an increase in its rate of synthesis, which, in turn, is associated with increased fibrinogen levels. Thus, both inflammation and plasma volume expansion factors that reduce albumin concentration and are independent cardiovascular risk factors, independently increase fibrinogen levels.     

Altered coagulation after albumin supplements for treatment of oligemic shock.

Coagulation and need for postoperative blood and plasma therapy were studied in 94 injured patients requiring massive transfusions (average = 14.4); 46 patients, by random selection, received supplemental albumin. Albumin therapy increased total protein concentration (6.4 vs 5.8 g/dL), serum albumin level (4.2 vs 2.9 g/dL), and plasma volume (3,895 vs 3,579 mL) but not RBC volume (1,520 vs 1,530 mL). During the initial five postoperative days, patients receiving albumin required more transfusions (7.1 vs 3.8) and plasma (455 vs 317 mL). This increased need for blood and plasma correlated with a significant decrease in fibrinogen (238 vs 405 mg/dL) and prolongation of the prothrombin time (2.6 vs 1.4 seconds). The partial thromboplastin time was prolonged and the platelet concentration was decreased in albumin-treated patients, but not significantly. Deficiencies in specific coagulation factors have not yet been identified but are being studied. Impaired coagulation is another potential hazard of supplemental albumin therapy, which is probably contraindicated in injured patients.     

Leptin is a negative acute phase protein in chronic hemodialysis patients

BACKGROUND: Hypoalbuminemia strongly predicts death in hemodialysis patients and results from both inflammation and malnutrition. One potential link between malnutrition and inflammation is appetite suppression triggered by inflammation. Leptin is secreted by adipose tissue and suppresses appetite, and it is also a positive acute phase protein in the rat. Factored for body weight, leptin is known to be increased in hemodialysis patients, but its relationship to inflammation is unknown. METHODS: We examined the relationship between spontaneously occurring activation of the acute phase response and leptin levels in 29 chronic hemodialysis patients. Serum samples were obtained three times weekly for six weeks and then monthly from 29 chronic hemodialysis patients, and the levels of the positive acute phase proteins [C-reactive protein (CRP), alpha1-acid glycoprotein (alpha1 AG), serum amyloid A, ceruloplasmin] and the negative acute phase proteins (albumin and transferrin) as well as leptin and interleukin-6 (IL-6) were measured. RESULTS: Positive and negative acute phase proteins were evaluated at the maximum CRP (mean, 9.42 +/- 1.14 mg/dL) and minimum values (mean, 0.41 +/- 0.09 mg/dL). When CRP was elevated, leptin levels were significantly reduced, as were the negative acute phase proteins albumin and transferrin. Serum amyloid A, ceruloplasmin, alpha1 acid glycoprotein, and IL-6 were all significantly increased at the maximum CRP level, compatible with general activation of the acute phase response. The change in leptin correlated negatively with the change in CRP (R = 0.437, P = 0.018), as did changes in albumin (R = 0.620, P < 0.001). CONCLUSIONS: Leptin is not increased as a consequence of inflammation in hemodialysis patients, but behaves as a negative rather than as a positive acute phase protein. Inflammation is unlikely to reduce appetite in dialysis patients through a leptin-mediated mechanism.     

Determinants of serum albumin concentration analyzed in a large cohort of patients on maintenance hemodialysis.

OBJECTIVE: Serum albumin concentration is a powerful predictor of mortality in patients on chronic hemodialysis (CHD). This study sought to investigate variables associated with serum albumin concentration. DESIGN AND STUDY POPULATION: Cross-sectional study in prevalent chronic hemodialysis patients treated at the Renal Research Institute between July 1, 2005 and October 31, 2005. A total of 4,798 (2,199 females) patients were studied. MAIN OUTCOME MEASURES: Univariate and multivariate relationships of serum albumin concentration with age, sex, race (black, white, other), vascular access type (arteriovenous fistula/graft, catheter), white blood cells, neutrophils, lymphocytes, equilibrated normalized protein catabolic rate (enPCR), dialysis efficacy (eKdrt/V), hemoglobin, phosphate, bio-intact parathyroid hormone [bioPTH], creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). RESULTS: Age, access type, and variables of 3 domains, namely, nutrition (enPCR; creatinine), eKdrt/V, and inflammation (white blood cells; neutrophil:lymphocyte ratio; hemoglobin), were related to serum albumin. It is interesting to note that AST was the strongest negative predictor of albumin levels. CONCLUSION: In CHD patients, serum albumin concentration is defined by a complex interaction of inflammation, nutrition, and dialysis efficacy. The relationship between AST and albumin deserves additional study.     

Is Serum Albumin a Marker of Nutritional Status in Hemodialysis Patients without Evidence of Inflammation?

Hypoalbuminemia, a strong predictor of morbidity and mortality in hemodialysis patients, can be a consequence of a combination of malnutrition and inflammatory reactions. The purpose of this study was to analyze serum albumin as a marker of nutritional status in maintenance hemodialysis patients with no signs of inflammation. In a cross-sectional study, we selected 40 stable hemodialysis patients with normal levels of C-reactive protein (<0.8 mg/dL). The patients were classified as well nourished (65%) or malnourished (35%) according to the subjective global assessment. No significant differences were observed in serum albumin concentrations (immunoturbidimetric method) between well-nourished (4.3 +/- 0.3 g/dL) and malnourished (4.0 +/- 0.5 g/dL) patients, and the mean values were within the normal range in both groups. Albumin was inversely correlated with age (n=40; r=-0.32; P=0.02) and directly with energy intake (n=28; r=0.43; P=0.04). In this study, serum albumin did not discriminate well-nourished and malnourished hemodialysis patients without evidence of inflammation.     

Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients.

BACKGROUND: Cross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown. METHODS: To explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases. RESULTS: The overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001). CONCLUSIONS: Proxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and "malnutrition."     

Potential impact of nutritional intervention on end-stage renal disease hospitalization, death, and treatment costs.

OBJECTIVE: Our objective was to estimate the effect of an improvement in nutrition, represented by albumin concentrations, on hospitalization, mortality, and Medicare end-stage renal disease (ESRD) program cost. DESIGN: Based on published trials, the impact of an improvement in serum albumin of +0.2 g/dL from a hypothetical nutritional program for severely malnourished patients with albumin < or = 3.5 g/dL (base case) was estimated by reassigning patients to higher albumin categories, along with outcome risks associated with the new albumin category. SETTING: Data from Fresenius Medical Care North America (Waltham, MA) were utilized in regression models to determine the association between albumin and change in albumin concentration with outcomes. RESULTS: Albumin < or = 3.5 g/dL was associated with a > 2-fold increase in death and hospitalization risk, compared to > or = 4 g/dL (P < .001) in this population. An increase in albumin concentration was associated with a lower risk of death and hospitalization, whereas a declining albumin concentration led to worse outcomes. Projections for the United States dialysis population from the base case showed approximately 1400 lives saved, approximately 6000 hospitalizations averted, and approximately $36 million in Medicare cost savings resulting from a reduction of approximately 20,000 hospital days. A sensitivity analysis, varying the albumin response to +0.1 and +0.3 g/dL combined with varying albumin responder rates to 25% and 75% of patients, revealed robust results. CONCLUSION: Nutritional interventions that increase serum albumin by > or = 0.2 g/dL (e.g., via oral nutritional supplements) may lead to considerable improvements in mortality, hospitalization, and treatment costs.     

Effects of long-term low protein diet on albumin metabolism in chronic uremia.

The effects of long-term low protein diet on albumin metabolism of uremic patients were evaluated. Studies were performed on 62 patients divided into two groups depending on the duration of the diet (35 subjects from 6 to 30 days, 27 subjects from 6 months to 5 years). All patients received a diet containing at least 20 g of high biological value proteins per day. Albumin catabolism and distribution were measured by the two-tracer technique, after simultaneous i.v. injection of 131I-human serum albumin and of free 125I-iodide. Albumin synthesis was directly determined in 10 patients by two tracers, 14C-carbonate and 131I-albumin, according to the xanthydrol technique for specific activities of urea and albumin guanido carbon in plasma. The main features of albumin metabolism observed in both groups studied were: normal intravascular albumin mass, marked reduction of extravascular and total albumin pools, with proportionally reduced catabolism. No significant turnover difference was found between the first group and the patients on diet from 0.5 to 5 years, thus suggesting that dietary treatment per se is not responsible for the albumin depletion observed in chronic uremia.     

The effect of serum albumin level on iron-induced oxidative stress in chronic renal failure patients

BACKGROUND: Intravenous iron (IVIR) administration is widely used to treat anemia in chronic renal failure (CRF) patients and causes oxidative stress. Despite the fact that proteins are extremely susceptible to oxidative stress, there have been no studies investigating the relationship between the severity of iron-induced acute oxidative stress and serum albumin. Therefore, we wanted to investigate the relation between the severity of iron-induced acute oxidative stress and serum albumin level in CRF patients. METHODS: A total of 68 patients (22 on hemodialysis, 24 on continuous ambulatory peritoneal dialysis and 22 predialytic CRF) with absolute iron deficiency were included to the study. Patients with acute inflammatory status, serum ferritin level > or = 100 ng/mL, transferrin saturation > or = 20%, hemoglobin level > or = 12 g/dL or serum C-reactive protein (CRP) level > or = 10 mg/dL were excluded. Serum direct 8-isoprostoglandin F2 alpha (IsoPG-F2 alpha) level was used as an oxidative stress marker. After baseline sampling, 100 mg ferric sucrose was infused within 30 minutes. Blood samples were drawn to assess changes in oxidative stress marker at the end of the IVIR infusion and at 240 minutes. Patients with serum albumin level <4 g/dL were defined as hypoalbuminemic and > or = 4 g/dL as normoalbuminemic. RESULTS: There were 34 hypoalbuminemic and 34 normoalbuminemic patients. Serum IsoPG-F2 alpha level increased in all patients after the administration of IVIR. The severity of iron-induced acute oxidative stress was more prominent in patients with a low serum albumin level. Serum albumin level, presence of diabetes mellitus (DM) and hemoglobin level were found as significant predictors of time-dependent changes in serum IsoPG-F2 alpha level. When the analyses were repeated in nondiabetic patients, serum albumin level was similarly found to be a significant predictor of time-dependent changes in serum IsoPG-F2 alpha level. CONCLUSION: This study demonstrated a negative interaction between iron-induced acute oxidative stress and serum albumin level in CRF patients. Because CRF patients with low serum albumin level are at greater risk for iron-induced acute oxidative stress, new strategies are necessary in this population.     

复杂腹腔感染对白蛋白合成速率的影响

目的探讨复杂腹腔感染对白蛋白合成速率的影响。方法前瞻陆收集2009年12月至2010年10月间南京军区南京总医院普通外科研究所收治的肠瘘合并复杂腹腔感染病例（感染组,8例）;另选取同期8名年龄、性别、BMI相匹配的健康志愿者作为对照组。受试者在空腹状态下经外周静脉给予首剂量无菌L-[ring-^2H5]-苯丙氨酸溶液（4μmol／kg）,继之以6μmol·kg^-1·h^-1的速度持续输注6h。输注前和输注后的每小时取3ml动脉血：通过GC-MS测定血浆游离氨基酸和掺入到白蛋白中L-[ring^2H5]．苯丙氨酸的同位素丰度。结果感染组患者血清总蛋白和白蛋白浓度分别为（62．2±1．0）g／L和（32．5±4．0）g／L,显著低于对照组[（74．2±1．7）g／L和（46．1±2．6）g／L;均P〈0．05]。感染组患者C反应蛋白、白细胞计数和体温3项全身炎性反应指标均高于对照组（均P〈0．05）。感染组患者白蛋白合成速率为（5．3±1．6）％／d,显著低于正常对照组的（7．8±1．2）％／d,差异有统计学意义（P〈0．05）。血浆游离氨基酸谱显示,感染组患者血浆谷氨酸高于对照组．苯丙氨酸和脯氨酸低于对照组（均P〈0．05）。结论复杂腹腔感染可明显抑制白蛋白合成,是腹腔感染患者低白蛋白血症的原因之一。     

Serum albumin: relationship to inflammation and nutrition

Hypoalbuminemia is the result of the combined effects of inflammation and inadequate protein and caloric intake in patients with chronic disease such as chronic renal failure. Inflammation and malnutrition both reduce albumin concentration by decreasing its rate of synthesis, while inflammation alone is associated with a greater fractional catabolic rate (FCR) and, when extreme, increased transfer of albumin out of the vascular compartment. A vicious cascade of events ensues in which inflammation induces anorexia and reduces the effective use of dietary protein and energy intake and augments catabolism of the key somatic protein, albumin. Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure, and the major cause of death in this population is due to cardiovascular events. Inflammation is associated with vascular disease and likely causes injury to the vascular endothelium, and hypoalbuminemia as two separate expressions of the inflammatory process. Albumin has a myriad of important physiologic effects that are essential for normal health. However, simply administering albumin to critically ill patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity. Thus the inference from these clinical studies suggests that the cause of hypoalbuminemia, rather than low albumin levels specifically, is responsible for morbidity and mortality.     

Nutrition counseling impacts serum albumin levels.

OBJECTIVE: To determine the difference in the rate of change of serum albumin levels between protein-energy malnourished patients who receive intensive dietary counseling and patients who receive a special oral liquid nutritional supplement (Nepro; Ross Products, Division Abbott Laboratories, Columbus, OH). DESIGN: Participants with serum albumin values < or =3.5 g/dL (bromocresol green) or 3.2 g/dL (bromocresol purple) and a Mini Nutrition Assessment (MNA) Malnutrition score < or =23.5 were randomized to the supplement group (Nepro) or the nonsupplement group with intensive dietary counseling. PATIENTS: Forty-one hemodialysis patients 18 years and older who had been on dialysis for at least 6 months. INTERVENTION: Participants were randomly assigned to supplement (26) or nonsupplement (14) groups. MAIN OUTCOME MEASURES: Albumin levels. STATISTICAL ANALYSES PERFORMED: Analysis of variance and chi2 tests, linear regression. RESULTS: After adjustment for demographic and clinical characteristics, the rate of change in serum albumin level was significantly greater among patients randomized to dietary counseling alone than among those who received oral supplements. These preliminary results suggest that intensive nutritional counseling may be of greater benefit than nutritional supplements alone in the management of protein-energy malnutrition in patients on hemodialysis. These preliminary findings should be confirmed by a larger full-scale trial.     

Correction of metabolic acidosis and its effect on albumin in chronic hemodialysis patients

Serum albumin concentration has been strongly associated with risk of death in hemodialysis patients, with mortality increasing as albumin decreases. Metabolic acidosis stimulates protein catabolism and decreases protein synthesis. A study was undertaken to investigate the effect of increasing predialysis serum bicarbonate (HCO3) concentrations on the nutrition of hemodialysis patients as measured by albumin and total lymphocyte count (TLC). Metabolic acidosis was defined as a predialysis serum bicarbonate concentration of < or = 18 mEq/L. Thirty-six hemodialysis patients were enrolled in the study. Each had been stable on hemodialysis for > or = 3 months and each had a mean serum bicarbonate concentration of < or = 18 mEq/L on predialysis monthly laboratory values during the preceding 3 months. The subjects were randomized into 2 groups. The first group consisted of 18 control subjects who were dialyzed on a standard bicarbonate bath of 35 mEq/L. The second group consisted of 18 experimental patients who were dialyzed on a bicarbonate bath of 40 mEq/L. Subjects in the experimental group who had predialysis serum bicarbonate concentrations less than 22 mEq/L after 2 weeks on the higher bicarbonate bath were additionally supplemented with oral sodium bicarbonate at a dosage of 1 mEq/kg dry weight/d. Monthly predialysis laboratory values were checked for all subjects and included serum electrolytes, blood urea nitrogen, calcium, and albumin. TLCs were obtained at the initiation and at the conclusion of the study. Intact parathyroid hormone, blood pressures, and interdialytic weight gains were also followed. The study lasted 16 weeks; 32 subjects completed the study (16 in each group). There were no statistically significant differences between the two groups at the initiation of the study. The serum bicarbonate concentrations were significantly different between the two groups at the end of the study (control HCO3 17.3 +/- 3.2 mEq/L v experimental HCO3 20.2 +/- 2.9 mEq/L; P = 0.01). Serum albumin concentrations and TLCs were not statistically different (P > 0.05) between the two groups at the end of the study (control albumin 3.88 +/- 0.28 g/dL v experimental albumin 3.76 +/- 0.26 g/dL and control TLC 1,780.0 +/- 779.4/mm3 v experimental TLC 2,020.1 +/- 888.0/mm3). Potassium, intact parathyroid hormone, interdialytic weight gain, blood pressures, Kt/Vs, and protein catabolic rates did not differ. We found that the change in serum bicarbonate concentration was well-tolerated and was without any demonstrable side effects. We conclude that increasing the serum bicarbonate concentration by 3 mEq/L for 16 weeks has no effect on the indicators of nutrition that we measured (serum albumin and TLC).     

Discrepancies in serum albumin measurements vary by dialysis modality

BACKGROUND: Serum albumin level is an important prognostic marker in patients with chronic renal failure. However there are discrepancies in the methods of estimation of serum albumin. The objective of this study is to evaluate the magnitude of the discrepancy in the serum albumin levels as measured by Bromcresol Green (BCG) and Bromcresol Purple (BCP) dye methods in patients on hemodialysis (HD) and peritoneal dialysis (PD) and to ascertain the clinical determinants of the discrepancy (deltaSA = BCG-BCP; g/dL) in each of the modalities. METHOD: We measured serum and plasma albumin levels by BCG and BCP methods in 19 adult HD patients and 18 adult PD patients treated in the dialysis units of the University of Colorado Health Sciences Center. Similar measurements were performed in 10 normal adult subjects. In all groups, paired blood samples were taken to estimate the albumin in both serum and plasma. Nephelometry (NM) was subsequently performed on the serum of 13 of the HD patients, 14 of the PD patients, and each of the 10 normal subjects. RESULTS: We found that for both the dye methods serum and plasma albumin levels are almost identical in each of the three subject groups. In the normal subjects serum albumin estimated by BCP is in good agreement with NM values but BCG overestimates the albumin levels. In the PD group the discrepancy between the BCG and BCP (deltaSA) is statistically significant with the BCG averaging 0.59 +/- 0.12 g/dL more than the BCP. The BCG values are closer to those obtained by the "gold standard", NM. In the HD group the deltaSA is significantly (p < 0.001) less than in the PD group (0.34 +/- 0.11 g/dL). As for PD, BCG values are closer to NM values. Increasing age, female gender, and higher dialysis adequacy are associated with higher deltaSA in the HD but not in the PD group. Utilizing linear regression analysis we developed equations for each dialysis modality to convert albumin measurements from one method to the other. CONCLUSION: We confirm that a discrepancy exists between the commonly used dye methods (BCG and BCP) for serum albumin estimation. This discrepancy is significantly lower in HD patients than in PD patients. Nephrologists should be aware of this discrepancy and appropriate corrections should be made during quality improvement analysis.     

Albumin synthesis, albuminuria and hyperlipemia in nephrotic patients

Hyperlipemia is a common manifestation of the nephrotic syndrome. Serum lipid concentrations have been observed by others to be negatively correlated with serum protein concentration. Hyperlipemia has been postulated to result from a coordinate increase in the synthesis of both albumin and lipoproteins, as well as from their decreased catabolism. Simultaneous measurements of serum lipid concentration and the rate of albumin synthesis have not been previously reported. We measured the rate of albumin synthesis, urinary albumin loss, serum albumin, protein, cholesterol and triglyceride concentration in 13 nephrotic patients. Changes in the rate of albumin synthesis and in urinary albumin excretion were induced in eight patients by alteration in dietary protein intake. The resultant changes in serum triglyceride and cholesterol were analyzed by multiple regression analysis. The rate of albumin synthesis measured while patients were eating a low protein diet was 12.61 +/- 1.20 g/1.73 m2/day, well within normal limits, yet both serum triglyceride and cholesterol concentrations were markedly elevated (265 +/- 65 mg/dl and 325 +/- 44 mg/dl, respectively). Albumin synthetic rate increased to 17.60 +/- 1.25 g/1.73 m2/day when dietary protein intake was increased, while serum triglyceride and cholesterol concentrations changed little; triglyceride concentration was 306 +/- 75 mg/dl and cholesterol 376 +/- 55 mg/dl. Serum cholesterol concentration, by multiple regression analysis, was dependent only upon the renal clearance of albumin P less than 0.0001, and changes in serum cholesterol concentration was dependent only upon changes in the renal clearance of albumin, P less than 0.001. Serum cholesterol concentration was completely independent of the rate of albumin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased albumin and fibrinogen synthesis in hemodialysis patients with normal nutritional status

This study compared the rates of whole-body proteolysis and of albumin and fibrinogen synthesis of seven hemodialysis patients (HD) with those of seven normal matched control subjects (C). HD patients had a normal nutritional and inflammatory status and serum albumin levels >3.5 g/dl. Endogenous leucine flux, albumin and fibrinogen fractional synthesis rate (FSR), and absolute intravascular synthesis rate (ASR) of albumin and fibrinogen all were evaluated by a primed/continuous infusion of 5,5,5-D3-L-leucine. Plasma volume was determined by the Evans blue dye dilution method. Endogenous leucine flux was significantly increased in HD (2.64 +/- 0.08 micromol/kg per min) compared with C (2.17 +/- 0.07 micromol/kg per min, P: < 0.05). Serum albumin concentrations were similar in HD and C. Plasma fibrinogen levels were significantly increased in HD compared with C (P: < 0.05). Plasma volume was greater in HD than in C (P: < 0.05). As a result, total intravascular pool of both albumin (141 +/- 7 versus 114 +/- 3 g/1.73 m(2), P: < 0.05) and fibrinogen (11.7 +/- 1 versus 6.7 +/- 0.5 g/1.73 m(2), P: < 0.05) were greater in HD than in C. Albumin FSR was not statistically different in HD and C. However, albumin ASR was significantly increased in HD than in C (13.7 +/- 2 versus 10.3 +/- 1 g/1.73 m(2) per d, P: < 0.05). Similarly, FSR of fibrinogen did not differ in HD and C groups, whereas ASR of fibrinogen was significantly higher in HD than in C (3.31 +/- 0.6 versus 1.94 +/- 0.3 g/1.73 m(2) per d, P: < 0.05). In summary, normoalbuminemic HD patients have an increased intravascular pool with a greater absolute synthesis rate of both albumin and fibrinogen and an increased rate of whole-body leucine flux.     

Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease

BACKGROUND: Low serum albumin is a strong risk factor for mortality, but its association with low serum bicarbonate and inflammation in the setting of mild to moderately decreased kidney function is uncertain. METHODS: We analyzed data from 15594 subjects over the age of 20 who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Glomerular filtration rate (GFR) in mL/min/1.73 m2 was estimated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation using appropriately calibrated serum creatinine. RESULTS: The age-adjusted prevalence of hypoalbuminemia (serum albumin <3.8 g/dL) at a GFR of 90, 60, 30, and 15 mL/min/1.73 m2 was 19%, 21%, 38%, and 59%, respectively, while the age-adjusted prevalence of C-reactive protein (CRP) >or= 0.22 mg/dL was 36%, 44%, 69%, and 81%, respectively, both P trend <0.001. Age, female gender, non-Hispanic black compared with non-Hispanic white race, diabetes, hypertension, hepatitis C, urine albumin: creatinine ratio >1 g/g, dietary protein intake, dietary caloric intake, serum bicarbonate, CRP, and GFR category were all significant predictors of hypoalbuminemia on univariate analysis. On simultaneously adjusting for the above variables, hypertension, diabetes, GFR, and dietary protein and caloric intake were no longer significant independent predictors of hypoalbuminemia. The adjusted odds ratio (OR) of serum bicarbonate (by quartile) for hypoalbuminemia was 1.0 for serum bicarbonate >28 mEq/L (reference), 1.25 for 26-28 mEq/L, 1.51 for 23-25 mEq/L, and 1.54 for 1.0 mg/dL. CONCLUSION: Elevated CRP and low serum bicarbonate are independently associated with hypoalbuminemia, explaining much of the high prevalence of hypoalbuminemia in chronic kidney disease.