Review

Authors: Bruce A Molitoris, Ruben M Sandoval, Shiv Pratap S Yadav...

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

Review

Authors: Timo Mayerhöfer, Andrew D Shaw, Christian J Wiedermann...

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

Review

Authors: Jean-Louis Vincent, James A Russell, Matthias Jacob...

Albumin solutions have been used worldwide for the treatment of critically ill patients since they became commercially available in the 1940s. However, their use has become the subject of criticism and debate in more recent years. Importantly, all fluid solutions have potential benefits and drawbacks. Large multicenter randomized studies have provided valuable data regarding the safety of albumin solutions, and have begun to clarify which groups of patients are most likely to benefit from their use. However, many questions remain related to where exactly albumin fits within our fluid choices. Here, we briefly summarize some of the physiology and history of albumin use in intensive care before offering some evidence-based guidance for albumin use in critically ill patients.

Topics: Albumins; Brain Injuries; Clinical Trials as Topic; Cost-Benefit Analysis; Critical Care; Critical Illness; Fluid Therapy; History, 20th Century; Humans; Hypoalbuminemia; Resuscitation; Sepsis

PubMed: 25042164
DOI: 10.1186/cc13991

Comparative Study Meta-Analysis

Authors: Tao Han Lee, George Kuo, Chih-Hsiang Chang...

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

Review

Authors: Alessandra Spada, Jaber Emami, Jack A Tuszynski...

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

Review

Authors: Nijin Wu, Tiantian Liu, Miaomiao Tian...

Human serum albumins (HSAs) are synthesized in the liver and are the most abundant proteins in plasma of healthy human. They play an important role in the pathophysiological processes of the liver and even the whole organism. Previous studies have mainly focused on the regulation of HSAs' expression. However, with the progress of research in recent years, it has been found that the content of circulating albumin cannot fully reflect the biological function of albumin itself. Given the aforementioned fact, the concept of serum 'effective albumin concentration' has been proposed. It refers to the content of albumin that is structurally and functionally intact. Alterations in the molecular structure and function of albumin have been reported in a variety of diseases, including liver disease. Moreover, these changes have been verified to affect the progression of oxidative stress‑related diseases. However, the link between albumin structure and function has not been fully elaborated, and the mechanisms by which different forms of albumin affect disease also need to be further investigated. In this context, the present review mainly expounded the biological characteristics and functions of albumin, summarized the different types of post‑translational modification of albumin, and discussed their functional changes and possible mechanisms in non‑alcoholic fatty liver disease, alcoholic hepatitis, viral hepatitis and different stages of cirrhosis. This will help to improve understanding of the role of albumin in disease development and provide a more comprehensive physiological basis for it in disease treatment.

Topics: Humans; Albumins; Liver Cirrhosis; Serum Albumin; Serum Albumin, Human; Non-alcoholic Fatty Liver Disease

PubMed: 38099350
DOI: 10.3892/mmr.2023.13147

Randomized Controlled Trial

Authors: Etienne Macedo, Bethany Karl, Euyhyun Lee...

BACKGROUND

Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients.

METHODS

A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded.

RESULTS

Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011].

CONCLUSION

In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

Topics: Adult; Aged; Albumins; Dialysis; Female; Humans; Hypoalbuminemia; Hypotension; Male; Middle Aged; Prospective Studies

PubMed: 33407747
DOI: 10.1186/s13054-020-03441-0

Review

Authors: Alla Shevtsova, Iuliia Gordiienko, Viktoriia Tkachenko...

Albumin is one of the most abundant proteins in the body of mammals: about 40% of its pool is located in the intravascular space and the remainder is found in the interstitial space. The content of this multifunctional protein in blood is about 60-65% of total plasma proteins. A decrease in its synthesis or changes of functional activity can destabilize oncotic blood pressure, cause a violation of transporting hormones, fatty acids, metals, and drugs. Albumin properties change under ischemic attacks associated with oxidative stress, production of reactive oxygen species, and acidosis. Under these conditions, ischemia-modified albumin (IMA) is generated that has a reduced metal-binding capacity, especially for transition metals, such as copper, nickel, and cobalt. The method of determining the cobalt-binding capability of HSA was initially proposed to evaluate IMA level and then licensed as an ACB test for routine clinical analysis for myocardial ischemia. Subsequent studies have shown the viability of the ACB test in diagnosing other diseases associated with the development of oxidative stress. This review examines recent data on IMA generation mechanisms, describes principles, advantages, and limitations of methods for evaluation of IMA levels, and provides detailed analysis of its use in diagnostic and monitoring therapeutic efficacy in different diseases.

Topics: Albumins; Biomarkers; Humans; Ischemia

PubMed: 34336009
DOI: 10.1155/2021/9945424

Review

Authors: John Ong, Junzhe Zhao, Alexander W Justin...

Albumin, the most abundant plasma protein in mammals, is a versatile and easily obtainable biomaterial. It is pH and temperature responsive, dissolvable in high concentrations and gels readily in defined conditions. This versatility, together with its inexpensiveness and biocompatibility, makes albumin an attractive biomaterial for biomedical research and therapeutics. So far, clinical research in albumin has centered mainly on its use as a carrier molecule or nanoparticle to improve drug pharmacokinetics and delivery to target sites. In contrast, research in albumin-based hydrogels is less established albeit growing in interest over recent years. In this minireview, we report current literature and critically discuss the synthesis, mechanical properties, biological effects and uses, biodegradability and cost of albumin hydrogels as a xeno-free, customizable, and transplantable construct for tissue engineering and regenerative medicine.

Topics: Albumins; Animals; Cell Transplantation; Drug Carriers; Humans; Hydrogels; Nanoparticles; Regenerative Medicine

PubMed: 31520415
DOI: 10.1002/bit.27167

Review

Authors: Zicheng Liu, Daria Trifonova, Inna Tulaeva...

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