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Nephrology, Dialysis, Transplantation :... Jun 2023The administration of fluids is one of the most common interventions in the intensive care unit. The effects and side effects of intravenous fluids depend on the amount... (Review)
Review
The administration of fluids is one of the most common interventions in the intensive care unit. The effects and side effects of intravenous fluids depend on the amount administered and their specific composition. Intravenous fluid solutions are either considered crystalloids (for example 0.9% saline, lactated Ringer's solution) or colloids (artificial colloids such as gelatins, and albumin). This narrative review summarizes the physiological principles of fluid therapy and reviews the most important studies on crystalloids, artificial colloids and albumin in the context of critically ill patients.
Topics: Humans; Isotonic Solutions; Crystalloid Solutions; Albumins; Colloids; Intensive Care Units
PubMed: 36170962
DOI: 10.1093/ndt/gfac279 -
Physiological Reviews Oct 2022For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative... (Review)
Review
For nearly 50 years the proximal tubule (PT) has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes. Several genetic diseases, nonselective PT cell defects, chronic kidney disease (CKD), and acute PT injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PT injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism, and transcytosis are being reexamined with the use of techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multireceptor complex that mediates albumin binding and uptake and directs proteins for lysosomal degradation after endocytosis. Albumin transcytosis is mediated by a pH-dependent binding affinity to the neonatal Fc receptor (FcRn) in the endosomal compartments. This reclamation pathway rescues albumin from urinary losses and cellular catabolism, extending its serum half-life. Albumin that has been altered by oxidation, glycation, or carbamylation or because of other bound ligands that do not bind to FcRn traffics to the lysosome. This molecular sorting mechanism reclaims physiological albumin and eliminates potentially toxic albumin. The clinical importance of PT albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussion of genetic disorders and therapeutic considerations.
Topics: Albumins; Biological Transport; Endocytosis; Humans; Kidney Tubules, Proximal
PubMed: 35378997
DOI: 10.1152/physrev.00014.2021 -
Nutrition in Clinical Practice :... Oct 2022Sepsis is the dysregulated immune response to severe infection that is common and lethal among critically ill patients. Fluid administration is a common treatment for... (Review)
Review
Sepsis is the dysregulated immune response to severe infection that is common and lethal among critically ill patients. Fluid administration is a common treatment for hypotension and shock in early sepsis. Fluid therapy can also cause edema and organ dysfunction. Research on the best treatment strategies for sepsis has provided insights on the optimal timing, dose, and type of fluid to treat patients with sepsis. Initial research on early goal-directed therapy for sepsis included an initial bolus of 30 ml/kg of fluid, but more recent research has supported use of smaller volumes. After initial fluid resuscitation, minimizing additional fluid administration may be beneficial, but no single measure has been established as the best method to guide ongoing fluid management in sepsis. Dynamic measures of "fluid responsiveness" can predict which patients will experience an increase in cardiac output from a fluid bolus. Use of such a measure in clinical care remains limited by applicability to patient populations and uncertainty regarding the effect on clinical outcomes. Recent research informs the effect of fluid composition on outcomes for patients with sepsis. Current data support the use of balanced crystalloids, rather than saline, and the use of crystalloids, rather than semisynthetic colloids. The role for albumin administration in sepsis remains uncertain. Future research should focus on determining the optimal volume of fluid during sepsis resuscitation, the effectiveness of measures of "fluid responsiveness" in improving outcomes, the optimal composition of crystalloid solutions, the role of albumin, and the effects of "deresuscitation" after septic shock.
Topics: Albumins; Crystalloid Solutions; Fluid Therapy; Humans; Sepsis; Shock, Septic
PubMed: 35801708
DOI: 10.1002/ncp.10892 -
Frontiers in Immunology 2022Systemic immune-inflammation index (SII) is a novel inflammatory marker, and inflammation has been reported to be related with renal damage. We aimed to investigate the...
BACKGROUND
Systemic immune-inflammation index (SII) is a novel inflammatory marker, and inflammation has been reported to be related with renal damage. We aimed to investigate the possible relationship between SII and albuminuria.
METHODS
The present cross-sectional study was conducted among adults with complete data about SII and urinary albumin-to-creatinine ratio (ACR) in 2005-2018 National Health and Nutrition Examination Survey (NHANES). SII was calculated as the platelet count × neutrophil count/lymphocyte count. Albuminuria was defined as ACR >30mg/g. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between SII and albuminuria.
RESULTS
A total of 36,463 individuals were included in our analysis; 9.56% participants were categorized as having albuminuria overall and increased with the higher SII tertiles (tertile 1, 7.83%; tertile 2, 8.49%; tertile 3, 12.13%; p for trend <0.0001). Multivariable logistic regression showed that a higher SII level was associated with increased likelihood of albuminuria independently (OR = 1.31; 95% CI, 1.17-1.48, p<0.0001) after full adjustment. Subgroup analysis and interaction test showed that there was no significant dependence of gender, age, body mass index, hypertension, diabetes, non-alcoholic fatty liver disease, and estimated glomerular filtration rate (eGFR) on this positive association (all p for interaction >0.05).
CONCLUSIONS
SII was positively associated with increased urinary albumin excretion in US adults. Further large-scale prospective studies are still needed to analyze the role of SII in albuminuria.
Topics: Adult; Albumins; Albuminuria; Cross-Sectional Studies; Humans; Inflammation; Nutrition Surveys; Serum Albumin, Human
PubMed: 35386695
DOI: 10.3389/fimmu.2022.863640 -
Molecular Pharmaceutics May 2021Albumin is an appealing carrier in nanomedicine because of its unique features. First, it is the most abundant protein in plasma, endowing high biocompatibility,... (Review)
Review
Albumin is an appealing carrier in nanomedicine because of its unique features. First, it is the most abundant protein in plasma, endowing high biocompatibility, biodegradability, nonimmunogenicity, and safety for its clinical application. Second, albumin chemical structure and conformation allows interaction with many different drugs, potentially protecting them from elimination and metabolism , thus improving their pharmacokinetic properties. Finally, albumin can interact with receptors overexpressed in many diseased tissues and cells, providing a unique feature for active targeting of the disease site without the addition of specific ligands to the nanocarrier. For this reason, albumin, characterized by an extended serum half-life of around 19 days, has the potential of promoting half-life extension and targeted delivery of drugs. Therefore, this article focuses on the importance of albumin as a nanodrug delivery carrier for hydrophobic drugs, taking advantage of the passive as well as active targeting potential of this nanocarrier. Particular attention is paid to the breakthrough NAB-Technology, with emphasis on the advantages of Nab-Paclitaxel (Abraxane), compared to the solvent-based formulations of Paclitaxel, i.e., CrEL-paclitaxel (Taxol) in a clinical setting. Finally, the role of albumin in carrying anticancer compounds is depicted, with a particular focus on the albumin-based formulations that are currently undergoing clinical trials. The article sheds light on the power of an endogenous substance, such as albumin, as a drug delivery system, signifies the importance of the drug vehicle in drug performance in the biological systems, and highlights the possible future trends in the use of this drug delivery system.
Topics: Albumins; Animals; Antineoplastic Agents; Disease Models, Animal; Drug Carriers; Half-Life; Humans; Hydrophobic and Hydrophilic Interactions; Nanoparticles; Neoplasms; Paclitaxel; Serum Albumin, Human
PubMed: 33787270
DOI: 10.1021/acs.molpharmaceut.1c00046 -
World Journal of Gastroenterology Sep 2022Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or... (Review)
Review
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
Topics: Albumins; Ascites; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Peritonitis
PubMed: 36156923
DOI: 10.3748/wjg.v28.i33.4773 -
Journal of Nuclear Medicine : Official... Jun 2022Fibroblast activation protein (FAP) has become an attractive target for diagnosis and therapy, and a series of FAP inhibitor (FAPI)-based radiotracers has been developed...
Fibroblast activation protein (FAP) has become an attractive target for diagnosis and therapy, and a series of FAP inhibitor (FAPI)-based radiotracers has been developed and had excellent performance for diagnosis outcomes in clinical applications. Yet, their fast clearance and insufficient tumor retention have hampered their further clinical application in cancer treatment. In this study, we developed 2 albumin binder-conjugated FAPI radiotracers, TEFAPI-06 and TEFAPI-07. They were derived from FAPI-04 and were optimized by conjugating 2 types of well-studied albumin binders, 4-(-iodophenyl) butyric acid moiety (TEFAPI-06) and truncated Evans blue moiety (TEFAPI-07), to try to overcome the above limitations at the expense of prolonging the blood circulation. TEFAPI-06 and TEFAPI-07 were synthesized and labeled with Ga, Y, and Lu successfully. A series of cell assays was performed to identify the binding affinity and FAP specificity in vitro. PET imaging, SPECT imaging, and biodistribution studies were performed to evaluate the pharmacokinetics in pancreatic cancer patient-derived xenograft (PDX) animal models. The cancer treatment efficacy of Lu-TEFAPI-06 and Lu-TEFAPI-07 were evaluated in pancreatic cancer PDX-bearing mice. The binding affinities (dissociation constants) to FAP of Ga-TEFAPI-06 and Ga-TEFAPI-07 were 10.16 ± 2.56 nM and 7.81 ± 2.28 nM, respectively, which were comparable with that of Ga-FAPI-04. Comparative PET imaging of HT-1080-FAP and HT-1080 tumor-bearing mice and a blocking study showed the FAP-targeting ability in vivo of these 2 tracers. Compared with Lu-FAPI-04, PET imaging, SPECT imaging, and biodistribution studies of TEFAPI-06 and TEFAPI-07 demonstrated their remarkably enhanced tumor accumulation and retention, respectively. Notable tumor growth inhibition by Lu-TEFAPI-06 and Lu-TEFAPI-07 were observed, whereas the control group and the group treated by Lu-FAPI-04 showed a slight therapeutic effect. Two albumin binder-conjugated FAPI radiopharmaceuticals have been developed and evaluated in vitro and in vivo. Significantly improved tumor uptake and retention were observed, compared with the original FAPI tracer. Both Lu-TEFAPI-06 and Lu-TEFAPI-07 showed remarkable growth inhibition of PDX tumors, whereas the side effects were almost negligible, demonstrating that these radiopharmaceuticals are promising for further clinical translational studies.
Topics: Albumins; Animals; Cell Line, Tumor; Endopeptidases; Fibroblasts; Gallium Radioisotopes; Humans; Membrane Proteins; Mice; Pancreatic Neoplasms; Radiopharmaceuticals; Tissue Distribution
PubMed: 34593598
DOI: 10.2967/jnumed.121.262533 -
Clinical Journal of the American... May 2021Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume.... (Review)
Review
Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.
Topics: Acute Kidney Injury; Albumins; Hemofiltration; Humans; Hypotension; Infusions, Intravenous; Kidney Failure, Chronic; Renal Dialysis
PubMed: 33115729
DOI: 10.2215/CJN.09670620 -
PloS One 2021It has been a matter of much debate whether the co-administration of furosemide and albumin can achieve better diuresis and natriuresis than furosemide treatment alone.... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
It has been a matter of much debate whether the co-administration of furosemide and albumin can achieve better diuresis and natriuresis than furosemide treatment alone. There is inconsistency in published trials regarding the effect of this combination therapy. We, therefore, conducted this meta-analysis to explore the efficacy of furosemide and albumin co-administration and the factors potentially influencing the diuretic effect of such co-administration.
METHODS
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, Medline, and Cochrane databases. Prospective studies with adult populations which comparing the effect of furosemide and albumin co-administration with furosemide alone were included. The outcomes including diuretic effect and natriuresis effect measured by hourly urine output and hourly urine sodium excretion from both groups were extracted. Random effect model was applied for conducting meta-analysis. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity of treatment effects.
RESULTS
By including 13 studies with 422 participants, the meta-analysis revealed that furosemide with albumin co-administration increased urine output by 31.45 ml/hour and increased urine excretion by 1.76 mEq/hour in comparison to furosemide treatment alone. The diuretic effect of albumin and furosemide co-administration was better in participants with low baseline serum albumin levels (< 2.5 g/dL) and high prescribed albumin infusion doses (> 30 g), and the effect was more significant within 12 hours after administration. Diuretic effect of co-administration was better in those with baseline Cr > 1.2 mg/dL and natriuresis effect of co-administration was better in those with baseline eGFR < 60 ml/min/1.73m2.
CONCLUSION
Co-administration of furosemide with albumin might enhance diuresis and natriuresis effects than furosemide treatment alone but with high heterogeneity in treatment response. According to the present meta-analysis, combination therapy might provide advantages compared to the furosemide therapy alone in patients with baseline albumin levels lower than 2.5 g/dL or in patients receiving higher albumin infusion doses or in patients with impaired renal function. Owing to high heterogeneity and limited enrolled participants, further parallel randomized controlled trials are warranted to examine our outcome.
REGISTRATION
PROSEPRO ID: CRD42020211002; https://clinicaltrials.gov/.
Topics: Albumins; Diuretics; Drug Combinations; Furosemide; Humans; Nephrotic Syndrome; Randomized Controlled Trials as Topic
PubMed: 34851962
DOI: 10.1371/journal.pone.0260312 -
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