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European Journal of Internal Medicine Nov 2023Albumin is the most abundant circulating protein and provides about 70% of the plasma oncotic power. The molecule also carries many other biological functions (binding,... (Review)
Review
Albumin is the most abundant circulating protein and provides about 70% of the plasma oncotic power. The molecule also carries many other biological functions (binding, transport and detoxification of endogenous and exogenous compounds, antioxidation, and modulation of inflammatory and immune responses). Hypoalbuminemia is a frequent finding in many diseases, representing usually only a biomarker of poor prognosis rather than a primary pathophysiological event. Despite that, albumin is prescribed in many conditions based on the assumption that correction of hypoalbuminemia would lead to clinical benefits for the patients. Unfortunately, many of these indications are not supported by scientific evidence (or have been even disproved), so that a large part of albumin use is nowadays still inappropriate. Decompensated cirrhosis is the clinical area where albumin administration has been extensively studied and solid recommendations can be made. Besides prevention and treatment of acute complications, long-term albumin administration in patients with ascites has emerged in the last decade has a potential new disease-modifying treatment. In non-hepatological settings, albumin is widely used for fluid resuscitation in sepsis and critical illnesses, with no clear superiority over crystalloids. In many other conditions, scientific evidence supporting albumin prescription is weak or even absent. Thus, given its high cost and limited availability, action is needed to avoid the use of albumin for inappropriate and futile indications to ensure its availability in those conditions for which albumin has been demonstrated to have a real effectiveness and an advantage for the patient.
Topics: Humans; Hypoalbuminemia; Medical Futility; Albumins; Fluid Therapy; Internal Medicine; Liver Cirrhosis
PubMed: 37423819
DOI: 10.1016/j.ejim.2023.07.003 -
Journal of Intensive Care Medicine Aug 2023The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis.
MATERIALS AND METHODS
PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals.
RESULTS
Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; = .03), which was better than 4% to 5% albumin and crystalloid.
CONCLUSIONS
Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.
Topics: Humans; Shock, Septic; Crystalloid Solutions; Randomized Controlled Trials as Topic; Sepsis; Albumins
PubMed: 37078161
DOI: 10.1177/08850666231170778 -
Endocrine Regulations Jan 2023Diabetes mellitus is characterized by hyperglycemia and abnormalities in insulin secretion and function. This review article focuses on various liver parameters,... (Review)
Review
Diabetes mellitus is characterized by hyperglycemia and abnormalities in insulin secretion and function. This review article focuses on various liver parameters, including albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alpha fetoprotein (AFP), alpha 1 antitrypsin (AAT), ammonia, bilirubin, bile acid, gamma-glutamyl transferase (GGT), immunoglobulin, lactate dehydrogenase (LDH), and total protein. These parameters play significant roles in the development of different types of diabetes such as type 1 diabetes (T1DM), type 2 diabetes (T2DM) and gestational diabetes (GDM). The article highlights that low albumin levels may indicate inflammation, while increased ALT and AST levels are associated with liver inflammation or injury, particularly in non-alcoholic fatty liver disease (NAFLD). Elevated ALP levels can be influenced by liver inflammation, biliary dysfunction, or bone metabolism changes. High bilirubin levels are independently linked to albuminuria in T1DM and an increased risk of T2DM. Elevated GGT levels are proposed as markers of oxidative stress and liver dysfunction in T2DM. In GDM, decreased serum AFP levels may indicate impaired embryo growth. Decreased AFP levels in T2DM can hinder the detection of hepatocellular carcinoma. Hyperammonemia can cause encephalopathy in diabetic ketoacidosis, and children with T1DM and attention deficit hyperactivity disorder often exhibit higher ammonia levels. T2DM disrupts the regulation of nitrogen-related metabolites, leading to increased blood ammonia levels. Bile acids affect glucose regulation by activating receptors on cell surfaces and nuclei, and changes in bile acid metabolism are observed in T2DM. Increased LDH activity reflects metabolic disturbances in glucose utilization and lactate production, contributing to diabetic complications. Poor glycemic management may be associated with elevated levels of IgA and IgG serum antibodies, and increased immunoglobulin levels are also associated with T2DM.
Topics: Child; Female; Pregnancy; Humans; Diabetes Mellitus, Type 2; alpha-Fetoproteins; Diabetes Mellitus, Type 1; Ammonia; Liver; Diabetes, Gestational; Inflammation; Albumins
PubMed: 37715985
DOI: 10.2478/enr-2023-0024 -
European Journal of Nuclear Medicine... Aug 2023Fibroblast activation protein-α (FAP)-targeting radioligands have recently demonstrated high diagnostic potential. However, their therapeutic value is impaired by the...
Head-to-head comparison of different classes of FAP radioligands designed to increase tumor residence time: monomer, dimer, albumin binders, and small molecules vs peptides.
PURPOSE
Fibroblast activation protein-α (FAP)-targeting radioligands have recently demonstrated high diagnostic potential. However, their therapeutic value is impaired by the short tumor residence time. Several strategies have been tested to overcome this limitation, but a head-to-head comparison has never been done. With the aim to identify strengths and limitations of the suggested strategies, we compared the monomer FAPI-46 versus (a) its dimer (FAPI-46-F1D), (b) two albumin binders conjugates (FAPI-46-Ibu (ibuprofen) and FAPI-46-EB (Evans Blue)), and (c) cyclic peptide FAP-2286.
METHODS
Lu-labeled ligands were evaluated in vitro in cell lines with low (HT-1080.hFAP) and high (HEK-293.hFAP) humanFAP expression. SPECT/CT imaging and biodistribution studies were conducted in HT-1080.hFAP and HEK-293.hFAP xenografts. The areas under the curve (AUC) of the tumor uptake and tumor-to-critical-organs ratios and the absorbed doses were estimated.
RESULTS
Radioligands showed IC in the picomolar range. Striking differences were observed in vivo regarding tumor uptake, residence, specificity, and total body distribution. All [Lu]Lu-FAPI-46-based radioligands showed similar uptake between the two tumor models. [Lu]Lu-FAP-2286 showed higher uptake in HEK-293.hFAP and the least background. The AUC of the tumor uptake and absorbed dose was higher for [Lu]Lu-FAPI-46-F1D and the two albumin binder conjugates, [Lu]Lu-FAPI-46-Ibu and [Lu]Lu-FAPI-46-EB, in HT1080.hFAP xenografts and for [Lu]Lu-FAPI-46-EB and [Lu]Lu-FAP-2286 in HEK293.hFAP xenografts. The tumor-to-critical-organs AUC values and the absorbed doses were in favor of [Lu]Lu-FAP-2286, but tumor-to-kidneys.
CONCLUSION
The study indicated dimerization and cyclic peptide structures as promising strategies for prolonging tumor residence time, sparing healthy tissues. Albumin binding strategy outcome depended on the albumin binding moiety. The peptide showed advantages in terms of tumor-to-background ratios, besides tumor-to-kidneys, but its tumor uptake was FAP expression-dependent.
Topics: Humans; HEK293 Cells; Tissue Distribution; Cell Line, Tumor; Albumins; Peptides; Peptides, Cyclic; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes
PubMed: 37261473
DOI: 10.1007/s00259-023-06272-7 -
Frontiers in Immunology 2023Albumins from animals are highly cross-reactive allergens for patients suffering from immunoglobulin E (IgE)-mediated allergy. Approximately 20-30% of cat and dog... (Review)
Review
Albumins from animals are highly cross-reactive allergens for patients suffering from immunoglobulin E (IgE)-mediated allergy. Approximately 20-30% of cat and dog allergic patients show IgE reactivity and mount IgE-mediated allergic reactions to cat and dog albumin. It is astonishing that allergic patients can develop specific IgE responses against animal albumins because these proteins exhibit a more than 70% sequence identity to human serum albumin (HSA) which is the most abundant protein in the blood of the human body. The sequence identity of cat albumin (Fel d 2) and dog albumin (Can f 3) and HSA are 82% and 80%, respectively. Given the high degree of sequence identity between the latter two allergens and HSA one would expect that immunological tolerance would prohibit IgE sensitization to Fel d 2 and Can f 3. Here we discuss two possibilities for how IgE sensitization to Fel d 2 and Can f 3 may develop. One possibility is the failed development of immune tolerance in albumin-allergic patients whereas the other possibility is highly selective immune tolerance to HSA but not to Fel d 2 and Can f 3. If the first assumption is correct it should be possible to detect HSA-specific T cell responses and HSA-containing immune complexes in sensitized patients. In the latter scenario few differences in the sequences of Fel d 2 and Can f 3 as compared to HSA would be responsible for the development of selective T cell and B cell responses towards Fel d 2 as well as Can f 3. However, the immunological mechanisms of albumin sensitization have not yet been investigated in detail although this will be important for the development of allergen-specific prevention and allergen-specific immunotherapy (AIT) strategies for allergy to albumin.
Topics: Humans; Cats; Animals; Dogs; Albumins; Hypersensitivity; Allergens; Immunoglobulin E; Serum Albumin, Human
PubMed: 37928538
DOI: 10.3389/fimmu.2023.1241518 -
Clinical Chemistry Feb 2024Measurement of urine albumin is critical for diagnosis, risk classification, and monitoring of chronic kidney disease (CKD). Guidelines recommend clinical decision... (Review)
Review
BACKGROUND
Measurement of urine albumin is critical for diagnosis, risk classification, and monitoring of chronic kidney disease (CKD). Guidelines recommend clinical decision cutoffs for the urine albumin-to-creatinine ratio (ACR) of 30 and 300 mg/g (3 and 30 mg/mmol). However, differences among manufacturers' routine urine albumin measurement procedures have been found to exceed 40%, suggesting CKD diagnosis and risk classification may vary depending upon the specific measurement procedure implemented in the laboratory.
CONTENT
This review discusses urine albumin pathophysiology and clinical practice guideline recommendations for CKD. The review also provides recommendations for urine specimen collection and storage, and results reporting for the ACR. Recent advances in measurement techniques and development of reference systems intended to facilitate standardization of urine albumin measurements are reviewed.
SUMMARY
Urine albumin is an important measurement procedure used for diagnosis, risk classification, and management of CKD. Urine albumin results should be reported as the ACR using quantitative measurement procedures. Random urine collections used for albuminuria screening should be followed by confirmation with first morning void collections to reduce variation and increase diagnostic accuracy for urine albumin measurement. Most measurement procedures utilize immunoturbidimetric or immunonephelometric techniques. However, results vary significantly among measurement procedures, potentially resulting in differences in classification or risk assessment for CKD. The National Institute for Standards and Technology (NIST) and other laboratories are developing reference systems, including liquid chromatography-tandem mass spectrometry candidate reference measurement procedures and reference materials, to enable standardization of routine measurement procedures.
Topics: Humans; Creatinine; Urinalysis; Albuminuria; Renal Insufficiency, Chronic; Albumins
PubMed: 38321881
DOI: 10.1093/clinchem/hvad174 -
Clinical Gastroenterology and... Sep 2023Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis... (Review)
Review
BACKGROUND & AIMS
Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy.
METHODS
A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included.
RESULTS
Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure.
CONCLUSIONS
Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multicenter prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.
Topics: United States; Humans; Hepatorenal Syndrome; Terlipressin; Prospective Studies; Acute Kidney Injury; Vasoconstrictor Agents; Albumins; Multicenter Studies as Topic
PubMed: 37625864
DOI: 10.1016/j.cgh.2023.06.006 -
Gastroenterology Oct 2023Although transient bacteremia is common during dental and endoscopic procedures, infections developing during sterile diseases like acute pancreatitis (AP) can have...
BACKGROUND & AIMS
Although transient bacteremia is common during dental and endoscopic procedures, infections developing during sterile diseases like acute pancreatitis (AP) can have grave consequences. We examined how impaired bacterial clearance may cause this transition.
METHODS
Blood samples from patients with AP, normal controls, and rodents with pancreatitis or those administered different nonesterified fatty acids (NEFAs) were analyzed for albumin-unbound NEFAs, microbiome, and inflammatory cell injury. Macrophage uptake of unbound NEFAs using a novel coumarin tracer were done and the downstream effects-NEFA-membrane phospholipid (phosphatidylcholine) interactions-were studied on isothermal titration calorimetry.
RESULTS
Patients with infected AP had higher circulating unsaturated NEFAs; unbound NEFAs, including linoleic acid (LA) and oleic acid (OA); higher bacterial 16S DNA; mitochondrial DNA; altered β-diversity; enrichment in Pseudomonadales; and increased annexin V-positive myeloid (CD14) and CD3-positive T cells on admission. These, and increased circulating dead inflammatory cells, were also noted in rodents with unbound, unsaturated NEFAs. Isothermal titration calorimetry showed progressively stronger unbound LA interactions with aqueous media, phosphatidylcholine, cardiolipin, and albumin. Unbound NEFAs were taken into protein-free membranes, cells, and mitochondria, inducing voltage-dependent anion channel oligomerization, reducing ATP, and impairing phagocytosis. These were reversed by albumin. In vivo, unbound LA and OA increased bacterial loads and impaired phagocytosis, causing infection. LA and OA were more potent for these amphipathic interactions than the hydrophobic palmitic acid.
CONCLUSIONS
Release of stored LA and OA can increase their circulating unbound levels and cause amphipathic liponecrosis of immune cells via uptake by membrane phospholipids. This impairs bacterial clearance and causes infection during sterile inflammation.
Topics: Humans; Acute Disease; Pancreatitis; Fatty Acids, Nonesterified; Oleic Acid; Inflammation; Albumins; Phosphatidylcholines
PubMed: 37263302
DOI: 10.1053/j.gastro.2023.05.034 -
European Journal of Clinical... Oct 2023Systemic inflammation is closely associated with the development and progression of heart failure (HF), increasing vulnerability to thromboembolic events. This...
BACKGROUND
Systemic inflammation is closely associated with the development and progression of heart failure (HF), increasing vulnerability to thromboembolic events. This retrospective cohort study assessed the potential of the fibrinogen-to-albumin ratio (FAR), a new inflammatory biomarker, as a prognostic indicator for HF risk.
METHODS
One thousand one hundred and sixty six women and 826 men with a mean age of 70.70 ± 13.98 years were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV v2.0) database. Additionally, a second cohort was obtained, including 309 patients from the Second Affiliated Hospital of Wenzhou Medical University. The relationship between FAR and the prognosis of HF was evaluated using multivariate analysis, propensity score-matched analysis, and subgroup analysis.
RESULTS
Fibrinogen-to-albumin ratio was an independent risk factor for 90-day all-cause mortality (hazard ratio: 1.19; 95% confidence interval (CI): 1.01-1.40), 1-year all-cause mortality (hazard ratio: 1.23; 95% confidence interval: 1.06-1.41), and length of hospital stay (LOS) (β: 1.52; 95% CI: 0.67-2.37) in the MIMIC-IV dataset, even after adjusting for potential covariates. These findings were verified in the second cohort (β: 1.82; 95% CI: 0.33-3.31) and persisted after propensity score-matching and subgroup analysis. FAR was positively correlated with C-reactive protein, NT-proBNP, and Padua score. The correlation between FAR and NT-proBNP (R = .3026) was higher than with fibrinogen (R = .2576), albumin (R = -.1822), platelet-to-albumin ratio (R = .1170), and platelet-to-lymphocyte ratio (R = .1878) (p < .05).
CONCLUSIONS
Fibrinogen-to-albumin ratio is an independent risk prognostic factor for 90-day, 1-year all-cause mortality and LOS among HF patients. Inflammation and prothrombotic state may underlie the relationship between FAR and poor prognosis in HF.
Topics: Male; Humans; Female; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; Prognosis; Heart Failure; Albumins; Inflammation; Fibrinogen
PubMed: 37381635
DOI: 10.1111/eci.14049 -
Intensive Care Medicine Jun 2024This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on resuscitation fluids in adult...
PURPOSE
This is the first of three parts of the clinical practice guideline from the European Society of Intensive Care Medicine (ESICM) on resuscitation fluids in adult critically ill patients. This part addresses fluid choice and the other two will separately address fluid amount and fluid removal.
METHODS
This guideline was formulated by an international panel of clinical experts and methodologists. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was applied to evaluate the certainty of evidence and to move from evidence to decision.
RESULTS
For volume expansion, the guideline provides conditional recommendations for using crystalloids rather than albumin in critically ill patients in general (moderate certainty of evidence), in patients with sepsis (moderate certainty of evidence), in patients with acute respiratory failure (very low certainty of evidence) and in patients in the perioperative period and patients at risk for bleeding (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than albumin in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using albumin rather than crystalloids in patients with cirrhosis (very low certainty of evidence). The guideline provides conditional recommendations for using balanced crystalloids rather than isotonic saline in critically ill patients in general (low certainty of evidence), in patients with sepsis (low certainty of evidence) and in patients with kidney injury (very low certainty of evidence). There is a conditional recommendation for using isotonic saline rather than balanced crystalloids in patients with traumatic brain injury (very low certainty of evidence). There is a conditional recommendation for using isotonic crystalloids rather than small-volume hypertonic crystalloids in critically ill patients in general (very low certainty of evidence).
CONCLUSIONS
This guideline provides eleven recommendations to inform clinicians on resuscitation fluid choice in critically ill patients.
Topics: Humans; Fluid Therapy; Critical Illness; Adult; Critical Care; Crystalloid Solutions; Resuscitation; Europe; Albumins; Sepsis
PubMed: 38771364
DOI: 10.1007/s00134-024-07369-9