Lower Albumin Concentrations Research Articles

Pharmacokinetic Modelling of the Plasma Protein Binding of Mycophenolic Acid in Renal Transplant Recipients

Renal function and the plasma albumin concentration have been shown to correlate with clearance of total mycophenolic acid (MPA). The hypothesis for the underlying mechanism is that low plasma albumin concentrations and accumulation of the glucuronide metabolite of MPA (MPAG) decrease the binding of MPA to albumin. The subsequent increase in the unbound fraction (f(u)) of MPA (MPA(u)) produces an increase in total MPA (MPA(t)) clearance. This study aimed to develop an empirical population pharmacokinetic model to describe the relationships between renal function and albumin concentration and MPAG, MPA(u) and MPA(t), in order to provide insight into the mechanism by which renal function and plasma albumin affect the disposition of MPA. 774 MPA(t), 479 MPA(u) and 772 total MPAG (MPAG(t)) plasma concentrations were available from 88 renal transplant recipients on days 11 and 140 after transplantation. Data were analysed using non-linear mixed-effects modelling. Time profiles of MPA(u) and MPAG(t) concentrations were adequately described by two 2-compartment pharmacokinetic models with a link between the central compartments, representing the glucuronidation of MPA(u) to form MPAG. MPA(t) concentrations were modelled using: [MPA(t)] = [MPA(u)] + [MPA(u)] * theta(pb), with [MPA(u)] * theta(pb) representing the bound MPA concentration, where [MPA(t)], [MPA(u)] and theta(pb) represent MPA(t) concentration, MPA(u) concentration and a factor that correlates to the total number of protein binding places, respectively. According to this equation, f(u) = [MPA(u)]/[MPA(t)] = 1/(1 + theta(pb)) * theta(pb), and therefore [MPA(t)], was significantly and independently correlated with creatinine clearance (CL(CR)), the plasma albumin concentration and the MPAG(t) concentration (all p < 0.001). A reduction in CL(CR) from 60 to 25 mL/min correlated with an increase in f(u) from 2.7% to 3.5%, accumulation of MPAG(t) concentrations from 50 to 150 mg/L correlated with an increase in f(u) from 2.8% to 3.7%, and a decrease in plasma albumin concentration from 40 to 30 g/L correlated with an increase in f(u) from 2.6% to 3.5%. No significant correlations were detected between MPA(u) clearance and the plasma albumin concentration or CL(CR). The model shows that low CL(CR), low plasma albumin concentrations and high MPAG concentrations decrease MPA(t) exposure by affecting MPA binding to albumin.

Serum phosphate is an important determinant of corrected serum calcium in end‐stage kidney disease

Approximately 12% of bound blood calcium is linked to various anions including phosphate. In patients with end-stage kidney disease (ESKD), serum phosphate is highly variable. We propose that establishing a formula to calculate albumin- and phosphate-corrected total calcium would be more appropriate to estimate free calcium in ESKD patients. In 82 haemodialysis patients, serum ionized calcium (Ca(ion)) and pH were measured by blood gas analyser with ion-selective electrodes at the point-of-care, while bicarbonate, phosphate, albumin, magnesium and total calcium (Ca(tot)) were measured at the central laboratory. Linear regression analysis of measured variables was used to best fit adjusted calcium versus Ca(ion). The most parsimonious multiple linear regression model (r(2) = 0.81) of variables associated with Ca(ion) included Ca(tot) (coeff 0.820, P < 0.0001), albumin (coeff -0.016, P < 0.0001) and phosphate (coeff -0.063, P < 0.002). Modelling of available variables yielded the following equation to adjust calcium for albumin and phosphate: Ca(albPh) = Ca(tot) + (0.015 x (40 - [albumin]) + 0.07 x (1.5 - [phosphate])). At an ambient albumin of 40 g/L, Ca(albPh) would be 0.07 mmol/L lower than Ca(tot) for every mmol/L of phosphate. In vitro data using three different albumin levels and increasing phosphate concentrations demonstrated this relationship, with the slope of the phosphate effect being stronger at lower albumin concentrations. Because guidelines recommendations indicate that corrected serum calcium should be maintained within the normal range in ESKD patients, inclusion of phosphate to correct Ca(tot) in these patients may have clinical implications on the choice of phosphate binders and the prescription of vitamin D or calcimimetic agents.

Serum acute phase protein concentrations in dogs with hyperadrenocorticism with and without concurrent inflammatory conditions

Acute phase proteins (APPs) are promising markers of inflammation in dogs, because they are more sensitive than WBC counts in detecting clinical and subclinical inflammation. Endogenous corticosteroids can mask an acute phase response and make it more difficult to identify underlying inflammatory disease. The purpose of this study was to evaluate the acute phase protein response in dogs with spontaneous hyperadrenocorticism (HAC) with and without concurrent inflammatory conditions. Serum concentrations of C-reactive protein (CRP), haptoglobin (Hp), fibrinogen, and albumin were measured in 44 healthy adult dogs and 39 dogs with HAC; the HAC group was further divided into dogs with and without concurrent infection/inflammation. A fourth group of dogs with severe sepsis and without HAC was compared with the dogs with HAC and severe sepsis. Dogs with uncomplicated HAC had significantly higher Hp and fibrinogen concentrations compared with healthy control dogs (P<.001). Dogs with HAC and severe inflammatory disease also had significantly higher CRP and lower albumin concentrations than control dogs and dogs with HAC without concurrent inflammation. Dogs with sepsis but without HAC had significantly higher CRP concentrations than dogs with HAC and sepsis. Dogs with HAC had increases in the moderate APPs (Hp and fibrinogen), and no significant changes in CRP and albumin compared with healthy dogs. Although concurrent HAC appeared to blunt the CRP response in dogs with sepsis, increased serum CRP concentration in dogs with HAC is likely indicative of severe concurrent inflammation.

Predictors for cardiovascular morbidity and overall mortality in Tunisian ESRD patients: A six year prospective study

Objectives The study was aimed to test the predictive value of several potential cardiovascular factors and markers for non fatal cardiovascular events (CVE) and overall mortality in Tunisian patients with renal failure. Subjects and methods One hundred and fifteen renal failure patients were followed-up from 2000 to 2006. At enrollment, each patient underwent clinical examination and blood collection for analysis of lipid parameters, albumin, C reactive protein (CRP), parathyroid hormone (PTH), homocysteine and hemoglobin. Multivariate Cox regression models were applied to identify the predictors for non fatal CVE and overall mortality. Results During the follow up, seventeen patients were lost. Among the 98 remaining patients, 29 presented a non fatal CVE (21.5%) and 15 were deceased (11.1%). In univariate analyses, non fatal CVE were more frequent in smokers and in patients with high PTH concentrations and low HDL levels. Moreover, low albumin concentrations were univariately associated with overall mortality. In the multivariate analysis, non fatal CVE was significantly and independently associated with age [hazard ratio (95% confidence interval), 1.04 (1.01–1.08); p = 0.028] and the upper quartile of PTH concentrations [2.68 (1.24–5.81); p = 0.013]. Overall mortality was independently predicted by the bottom quartile of albumin concentrations [5.62 (2.02–15.6); p = 0.001] and the upper quartile of CRP concentrations [3.20 (1.14–8.79); p = 0.027]. Conclusion Advanced age and high PTH levels are the main predictors of CVE, whereas low albumin and high CRP concentrations are the independent predictors of death in Tunisian renal patients. A better control of these factors would greatly increase the patient's survival rates.

Validation of a simple method of estimating plasma free cortisol: Role of cortisol binding to albumin

Objectives: To develop, optimize, and validate a generalized mass action, equilibrium solution that incorporates measured concentrations of albumin as well as cortisol binding globulin (CBG) to estimate free cortisol. Design and methods: Free cortisol was estimated by Coolens method or by cubic equilibrium equation and compared to measured free cortisol, determined by ultrafiltration method, in subjects with septic shock ( n = 45), sepsis ( n = 19), and healthy controls ( n = 10) at 0, 30, and 60 min following administration of cosyntropin (250 mcg). The data set also included repeat testing in 30 subjects following recovery from sepsis/septic shock. The equilibrium dissociation constant for cortisol binding to albumin ( K A) was optimized by non-linear regression. The cubic equilibrium solution was also used to model the influence of cortisol, CBG, and albumin concentration on free cortisol. Results: Compared to measured free cortisol, the cubic solution, using an optimized K A of 137,800 nM, was less biased than Coolens solution, with mean percent error of − 23.0% vs. − 41.1% (paired t test, P < 0.001). Standard deviation values were also significantly lower (Wilks' test, P < 0.001) for the cubic solution (SD 35.8% vs. 40.8% for cubic vs. Coolens, respectively). Modeling studies using the cubic solution suggest an interaction effect by which low concentrations of CBG and albumin contribute to a greater increase in free cortisol than the sum of their independent effects. Conclusions: Mass action solutions that incorporate the measured concentration of albumin as well as CBG provide a reasonably accurate estimate of free cortisol that generalizes to conditions of health as well as a setting of hypercortisolism and low CBG and albumin concentrations associated with septic shock. Modeling studies emphasize the significant contribution of albumin deficiency and albumin-bound cortisol under conditions of CBG-deficiency, and identify a synergistic effect by which combined CBG and albumin deficiency contribute to elevation of free cortisol in septic shock.

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (P⩽0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer.

Transthyretin as a marker to predict outcome in critically ill patients

BackgroundA determination of serum Transthyretin (TTR, Prealbumin) level is an objective method of assessing protein catabolic loss of severely ill patients and numerous studies have shown that TTR levels correlate with patient outcomes of non-critically ill patients. We evaluated whether TTR level correlates with the prevalence of PEM in the ICU and evaluated serum TTR level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients. MethodsWe studied PEM prevalence in 118 patients admitted to a community hospital's medical intensive care unit and the association between TTR, low albumin (ALB) concentration and high-risk disease (HRD), i.e., sepsis, inability to take in oral nutrients, etc. Serum TTR was measured on the day of admission, day 3 and day 7 of their ICU stay. APACHE II and SOFA score was assessed on the day of admission and the nutritional status and nutritional requirement was assessed for their entire ICU stay. Patients were divided into three groups based on initial TTR level and the outcome analysis was performed for APACHE II score, SOFA score, ICU length of stay, hospital length of stay, and mortality. ResultsTTR showed excellent concordance with patients classified with PEM or at high malnutrition risk, and followed for 7 days, it is a measure of the metabolic burden. TTR levels decline from day 1 to day 7 in spite of providing nutritional support. Patients were classified in 3 categories with respect to the level of TTR: more than 170 mg/L, twenty-five patients (group 3); 100–170 mg/L, forty-eight patients (group 2); less than 100 mg/L, forty-five patients (group 1). TTR level correlated with ICU length of stay, hospital length of stay, and APACHE II score, and predicts mortality. ConclusionsTTR identified patients at highest risk for metabolic losses associated with stress hypermetabolism as serum TTR levels did not respond early to nutrition support because of the delayed return to anabolic status. It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition.

Mutations and polymorphisms of the gene of the major human blood protein, serum albumin

We have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin (ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations are included where observed. Most of the changes are benign. The majority of them were detected upon clinical electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in analbuminemia, defined as a serum albumin concentration of <1 g/L. These were generally detected upon finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts. Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation shows O-glycosylation.

Pitfalls of Measuring Total Blood Calcium in Patients with CKD

Disorders of mineral and bone metabolism are prevalent in patients with chronic kidney disease (CKD). The recent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend that blood calcium (Ca) be regularly measured in patients with stages 3 to 5 CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) position states that the measurement of ionized Ca (iCa) is preferred and that if total Ca (tCa) concentration is used instead, then it should be adjusted in the setting of hypoalbuminemia. In 691 consecutive patients with stages 3 to 5 CKD, we compared the ability of noncorrected and albumin-corrected tCa concentration to identify low, normal, or high iCa concentration. The agreement between noncorrected or albumin-corrected tCa and iCa was only fair. The risk for underestimating ionized calcium was independently increased by a low total CO(2) concentration when either noncorrected or albumin-corrected Ca was used and by a low albumin concentration only when noncorrected tCa was used. The risk for overestimating iCa was increased by a low albumin concentration only when albumin-corrected Ca was used. In conclusion, albumin-corrected tCa does not predict iCa better than noncorrected tCa. Moreover, both noncorrected and albumin-corrected tCa concentrations poorly predict hypo- or hypercalcemia in patients with CKD.

Influence of Composition, Concentration and Temperature of some Biological Liquids upon the Corrosion Behaviour of Titanum

In order to investigate the corrosion behaviour of titan in aqueous solutions of lactic acid (1, 3 and 4% w) and albumin (2 and 10 % w) the cyclic polarization curves in potentiodynamic conditions were used. The corrosion parameters were estimated and their values were discussed as a function of acid lactic and albumin concentration and temperature. The stability of titan in investigated biological liquids was interpreted by involvment of the adsorption of either lactic acid or albumin onto the passive layer, a process which is favorised by moderate temperatures (as 370C � the human body temperature) as well as by low concentrations of lactic acid and albumin, respectively.

Immune complex-mediated glomerulonephritis is ameliorated by thrombin-activatable fibrinolysis inhibitor deficiency

The activity of plasmin plays a critical role in the development of chronic glomerulonephritis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of plasmin generation. We hypothesized that TAFI is involved in the pathogenesis of glomerulonephritis because it inhibits plasmin generation. To demonstrate this hypothesis, we compared the development of immune complex-mediated glomerulonephritis in wild-type and TAFI-deficient mice. After six weeks of treatment with horse spleen apoferritin and lipoplysaccharide to induce glomerulonephritis, mice deficient in TAFI had significantly better renal function as shown by lower concentrations of albumin in urine and blood urea nitrogen compared to wild-type mice. In addition, the activity of plasmin and matrix metalloproteinases was significantly increased, and mesangial matrix expansion and the deposition of collagen and fibrin in kidney tissues were significantly decreased in TAFI-knockout mice as compared to their wild-type counterparts. Depletion of fibrinogen by batroxobin (Defibrase) treatment led to equalization of the renal function and the amount of collagen deposition in the kidneys of TAFI-knockout and wild-type mice with immune complex-mediated glomerulonephritis. Together these observations suggest that TAFI-mediated inhibition of plasmin generation plays a role in the pathogenesis of glomerulonephritis, and that it may constitute a novel molecular target for the therapy of this disease.

Use of Single-Value Protein Compensation of the Jaffe Creatinine Assay Contributes to Clinically Significant Inaccuracy in Results

Effective use of equations for calculating estimated glomerular filtration rate (eGFR) requires reliable plasma creatinine measurements (1). Considerable effort has been made to standardize calibration (2)(3), but standardization does not correct for analytical interferences, such as protein interference in Jaffe creatinine assays. A single-value correction factor is often used to correct for nonspecific protein interference in Jaffe assays, but this approach does not take into account differences in plasma albumin concentrations among samples. Because of the current interest in low creatinine results for calculation of eGFR, we evaluated the validity and clinical impact of using a single compensation value. We determined the dependence of creatinine results on albumin concentration by adding increasing amounts of human albumin powder to plasma specimens containing low albumin and creatinine concentrations of 50 and 340 μmol/L, respectively. We then measured, in …

Fibrogenesis in Fatty Liver Associated with Obesity and Diabetes Mellitus Type 2

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.

Analbuminemia Produced by a Novel Splicing Mutation

Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating human serum albumin in homozygous or compound heterozygous individuals. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was diagnosed in a Turkish female infant on the basis of low albumin concentration ( approximately 9.0 g/L). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and submitted to direct sequencing. The proband was found to be homozygous for a T-->C transition at nucleotide 13381, the 2nd base of intron 11. The effect of this previously unreported mutation, which inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of intron 11, was evaluated by examining the cDNA obtained by reverse transcription-PCR from the albumin mRNA extracted from the proband leukocytes. This analysis revealed that the mutation, named Bartin for the geographical origin of the patient's family, results in the skipping of exon 11. The subsequent frameshift within exon 12 originates a premature stop codon located 5 codons downstream at position 411. The predicted translation product would consist of 410 amino acids. This novel extensive cDNA alteration is responsible for the analbuminemic trait.

Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer

The relationship between the systemic inflammatory response (as evidenced by elevated C-reactive protein and lowered albumin concentrations), clinico-pathologic status and relapse-free, cancer-specific and overall survival was examined in patients with invasive primary operable breast cancer (n=300). The median follow-up of the survivors was 46 months. During this period, 37 patients relapsed and 25 died of their cancer. On multivariate analysis, only tumour size (P<0.05), albumin (P<0.01) and systemic treatment (P<0.0001) were significant independent predictors of relapse-free, cancer-specific and overall survival. Lower serum albumin concentrations (⩽43 g l−1) were associated with deprivation (P<0.05), hormonal receptor negative tumours (P<0.01) and significantly poorer 3-year relapse-free (85 vs 93%, P=0.001) cancer-specific (87 vs 97%, P<0.0001) and overall survival (84 vs 94%, P=0.001) rates. The results of the present study suggest that lower preoperative albumin concentrations, but not elevated C-reactive protein concentrations, predict relapse-free, cancer-specific and overall survival, independent of clinico-pathologic status and treatment in patients undergoing potentially curative surgery for primary operable breast cancer.

A Liquid Chromatography-Mass Spectrometry Method for the Quantification of Urinary Albumin using a Novel 15N-Isotopically Labeled Albumin Internal Standard

Recent studies suggest that microalbuminuria confers increased cardiovascular risk, even in nondiabetic and nonhypertensive persons (1)(2). Clinically, the testing of microalbuminuria uses immunochemical methods. Controversy exists, however, regarding the accuracy of immunochemical and chromatographic methods for quantifying urine albumin (3). We earlier reported on liquid chromatography-mass spectrometry (LC-MS) for measurement of urinary albumin with bovine serum albumin (BSA) as an internal standard (4). We now report the preparation of 15N-labeled albumin as an internal standard and the validation of its use in an LC-MS assay for quantifying low concentrations of albumin in the urine of patients. The Pichia pastoris strain GS115/His+Muts (Invitrogen) was used to synthesize 15N-labeled human serum albumin (HSA) [see details in the Data Supplement that accompanies the online version of this Letter at http://www.clinchem.org/content/vol53/issue3]. A Q-TOF Premier™ mass spectrometer (Waters/Micromass) was used to characterize the 15N-labeled HSA and study its fragmentation. Loo et al. (5) previously reported the generation of source-induced fragmentation of intact proteins in an electrospray ionization source of …

Determination of ximelagatran, melagatran and two intermediary metabolites in plasma by mixed-mode solid phase extraction and LC–MS/MS

An analytical method was developed for the determination of ximelagatran, an oral direct thrombin inhibitor, its active metabolite melagatran, and the two intermediate metabolites, OH-melagatran and ethyl-melagatran in human plasma. Extraction of plasma was carried out on a mixed mode bonded sorbent material (C8/SO 3 −). All four analytes, including their isotope-labelled internal standards, were eluted at high ionic strength with a mixture of 50% methanol and 50% buffer (0.25 M ammonium acetate and 0.05 M formic acid, pH 5.3) with an extraction recovery above 80%. The extracts were demonstrated to be clean in terms of a low concentration of albumin and lysoPC. The sample extraction was fully automated and performed in 96-well plates using a Tecan Genesis pipetting robot. Analysis of the extracts were performed with liquid chromatography followed by positive electrospray ionization mass spectrometry. The low organic content and the low pH of the extracts allowed for, after dilution 1:3 with buffer, direct injection onto the LC-column. The four analytes were separated on a C18 analytical LC-column using gradient elution with the acetonitrile concentration varying from 10 to 30% (v/v) and the ammonium acetate and acetic acid concentration kept constant at 10 and 5 mmol/L, respectively, at a flow rate of 0.75 mL/min. Linearity was achieved over the calibrated range 0.010–4.0 μmol/L with accuracy and relative standard deviation in the range 96.9–101.2% and 6.6–17.1%, respectively at LLOQ, and in the range 94.7–102.6% and 2.7–6.8%, respectively at concentrations above 3 × LLOQ. The method replaces a manual method, and displays the advantages of having a fully automated sample clean-up, no evaporation/reconstitution step, high recovery, and complete LC-separation of all four analytes.

Effect of albumin concentration on serum cortisol measured by the Bayer Advia Centaur assay

A poor comparison was seen between the Bayer Advia Centaur and the Roche Elecsys cortisol methods using samples sent to the laboratory for cortisol analysis. They were predominantly from patients attending the Endocrine outpatients clinic or patients in the intensive therapy unit. We investigated the effect of albumin concentration on the performance of both assays. For the samples used in the patient comparison, the laboratory database was searched for any concomitant albumin concentrations (Beckman LX20 BCP method). A series of recovery experiments were performed combining samples with normal albumin and undetectable cortisol concentrations with samples with detectable cortisol but low albumin concentrations. Albumin concentration accounts for almost 50% of the variation in the difference between the two methods. The Bayer Advia Centaur method shows significant under-recovery at albumin concentrations lower than 24 g/L. This under-recovery will significantly affect the diagnosis of adrenal insufficiency in critically ill patients with low albumin concentrations.

Micronutrient status during lactation in HIV-infected and HIV-uninfected South African women during the first 6 mo after delivery

Background: Little information on the micronutrient status of HIV-infected (HIV-positive) breastfeeding women is available.Objective: The objective was to compare the protein and micronutrient status of South African breastfeeding women by HIV status.Design: Serum albumin, prealbumin, vitamin B-12, folate, retinol, α-tocopherol, hemoglobin, ferritin, and zinc concentrations were compared between 92 HIV-positive and 52 HIV-uninfected (HIV-negative) mothers 6, 14, and 24 wk after delivery. C-reactive protein and α1-acid glycoprotein were used as proxy indicators of an inflammatory process.Results: Mean albumin and prealbumin were significantly lower in HIV-positive mothers, and a higher proportion of HIV-positive mothers had low albumin concentrations (<35 g/L). Less than 45% of the mothers were vitamin B-12 or folate sufficient. Significantly more HIV-positive (70.5%) than HIV-negative (46.2%) mothers had marginal vitamin B-12 status (P < 0.05), and mean folate concentrations were lower in HIV-positive mothers (P = 0.05). Mean serum retinol was significantly lower in HIV-positive mothers, even after control for the acute phase response. At 24 wk, 70% of both groups had an α-tocopherol deficiency (<11.6 μmol/L), but no significant difference by HIV status was observed. More HIV-positive (33.3%) than HIV-negative (8.7%) mothers had anemia (P = 0.018), whereas 25% of all mothers had low serum ferritin concentrations. After the acute phase response was controlled for, zinc deficiency was more common in HIV-positive (45.0%) than in HIV-negative (25.0%) mothers (P = 0.05).Conclusions: Deficiencies in vitamins B-12, folate, α-tocopherol, ferritin, and zinc are common in South African breastfeeding mothers. HIV-positive mothers had lower mean serum concentrations of albumin, prealbumin, folate, retinol, and hemoglobin than did HIV-negative mothers.

A new formula for correction of total calcium level into ionized serum calcium values in very elderly hospitalized patients

Ionized calcium (Ca 2+) seems to be the best measure of active serum calcium but, in France, numerous laboratories do not have Ca 2+ analyzers so that numerous clinicians use Payne's formula to obtain adjusted calcium (Ca Ad) values. In frail very elderly patients with protein/energetic malnutrition and very low concentrations of albumin, “correction” with Payne's formula usually gives false hypercalcemic results, so that hypocalcemia may be seriously underdiagnosed. Two hundred and ninety-four patients of 80 years and older with serum albumin level <35 g/l were included in four French hospitals for elderly people. Biological measurements were standardized in order to determine Ca 2+ and total calcium (Ca T) in accordance with approved guidelines. Ca Ad was calculated with Payne's formula whereas the dependence of Ca 2+ with serum protein, albumin and Ca Ad was investigated by linear regression, the goodness-of-fit of each equation with the measure of Ca 2+ being studied. Taking into account serum protein and albumin levels, multiple linear regression gave the equation: Ca 2+ (mmol/l) = 0.188 − 0.00469 protein (g/l) + 0.0110 albumin (g/l) + 0.401Ca Ad with r 2 = 0.442. The relative difference between the measure and the value given by the equation did not depend upon the center, and the correlation between measured and computed values of Ca 2+ was better, for any group, with our formula than with Payne's formula. When Ca 2+ was expressed with Ca T instead of Ca Ad, albumin term was no longer significant and the new equation was: Ca 2+ (mmol/l) = 0.592 − 0.00449 protein (g/l) + 0.410 total calcium (mmol/l) with r 2 = 0.438. We propose an alternative to direct measurement of Ca 2+ with a simple formula usable in geriatric units, which are often deprived of high-performance equipment.