Documente Academic
Documente Profesional
Documente Cultură
DOI: 10.12659/AOT.889188
Received: 2013.02.20
Accepted: 2013.03.20
Published: 2013.05.10
WWW.annalsoftransplantation.COM
Review Paper
Summary
Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather
than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function.
In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications
has increased in recent years. This, along with increased costs of manufacturing and
lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices.
This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional
and governmental organizations. Results reflect current knowledge about the role
of albumin in health and disease and relevance of albumin therapy in specific clinical settings.
Key words:
Authors address:
Jacek Rozga, Department of Surgical & Transplantation Nursing, Medical University of Warsaw, Oczki 4 St.,
02-007 Warsaw, Poland, e-mail: jrozga@dslextreme.com
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Background
Human albumin has many important physiologic
effects and has been used in various clinical settings for 7 decades [14]. For example, it is commonly used in patients with a volume or oncotic
deficit, despite the fact that a large number of studies comparing albumin solution with other agents
for fluid resuscitation have failed to demonstrate
a beneficial effect of albumin [2]. Furthermore,
the safety record of albumin has been challenged
by Cochrane meta-analysis, where the risk of death
in patients receiving albumin solutions was found
to be greater than in patients who received no albumin [5]. Although this analysis received much
criticism and the authors conclusions about albumin were not confirmed in subsequent studies,
controversy about certain uses of albumin persist
to this day. Further focused clinical trials to evaluate the effectiveness and safety of albumin in critically ill patients are warranted [2,59].
The use of albumin solution in other clinical settings, such as decompensated cirrhosis, cirrhosis complicated by ascites, renal failure or spontaneous bacterial peritonitis, is less controversial
(1013]. Furthermore, over time, licensed indications for medical use of albumin have expanded (e.g., albumin dialysis). This, along with increased costs of manufacturing and decreased
production of albumin for medical uses, has
lead to an ongoing shortage and rapid increase
in the price of albumin (as high as $75/gram for
human recombinant product). In this situation,
it is reasonable to develop usage criteria, protocols, and guidelines for appropriate utilization
of albumin. This review aims to highlight the
relevance of albumin therapy in the context of
old, new, and emerging indications in the critically ill and in patients with failing liver, kidneys,
and other organs.
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Functions
Albumin is a major multifunctional protein. It accounts for 5560% of all plasma proteins and is
regarded as a negative acute-phase protein [15].
The physiological and pathophysiological functions of albumin in humans are relatively well
known, although the exact role in critical illnesses and certain chronic diseases is not fully understood and some authors believe they may differ
significantly from those seen in healthy subjects
[21]. Table 1 describes in an abbreviated form
the principal functions of albumin.
array of critical illnesses can result in and/or become exacerbated by low serum albumin. The
pathomechanism of hypoalbuminaemia is always
ascribed to one or more factors, such as malnutrition, changes in the rates of synthesis and
degradation of albumin, altered distribution between the intravascular and extravascular compartments, translocation of albumin molecules
into the extravascular compartment, changes
in albumin kinetics (transcapillary flow vs. lymphatic return), and external losses (e.g., burns
or hemorrhage) (Table 2).
Albumin Therapy
The first clinical use of human albumin dates
back to the attack on Pearl Harbor during World
War II, when it was used in several burned sailors
[4]. Three years later, Janeway et al reported using albumin in patients with decompensated liver
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Mechanisms
Sepsis
Cancer
Burns
Hemorrhage
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such as acute lung injury or acute respiratory distress syndrome, albumin therapy was found to improve oxygenation and hemodynamic status [64].
Surprisingly, there is only limited evidence to justify the use of human albumin in patients with
malnutrition, protein-losing entheropaties, and
malabsorption. Accordingly, albumin therapy is
not recommended in these patient populations
[54]. However, patients with severe diarrhea
who cannot tolerate enteral nutrition and do
not respond to short-chain peptides and mineral formulas, may benefit from albumin therapy
(Grade 2C recommendation). The effects of correcting hypoalbuminaemia in nephrotic syndrome
are short-lived, as most of the administered albumin is quickly eliminated by the kidneys.
Nonetheless, short-term infusion of 2025% albumin can be used in hypoalbuminemic patients
with hypovolemia and/or secondary complications (e.g., pulmonary oedema, acute pulmonary oedema, and/or acute renal failure (Grade
2C recommendation) [76].
Emerging medical uses of albumin
In keeping with the increasing knowledge about
albumin as the key blood component that binds,
inactivates, and transports blood-borne toxins to
other organs for metabolism and/or excretion,
albumin dialysis, large-pore hemofiltration, and
albumin exchange have emerged as liver support therapies [7784]. One of the key engineering features of some of these technologies (e.g.,
Prometheus, SEPET, Evaclio, SeptX) is
the use of a membrane permeable to albumin,
albumin-bound toxins, inflammatory mediators,
and other middle molecules [7880,83].
Albumin filtration and dialysis
Currently, there is no direct, satisfactory treatment for hepatic failure and patients must receive a transplant or endure prolonged hospitalization with significant morbidity and mortality.
Because of the scarcity of donor organs, many
liver failure patients will die awaiting a transplant. In addition, many patients do not qualify
for transplantation due to medical and socio-psychological reasons. Thus, liver support strategies
are being developed with the aim of either supporting patients until an appropriate organ becomes available for transplantation or until their
livers recover from injury (regenerate). Until the
1990s, hepatic failure was thought to be caused
by small water-soluble molecules and most liver
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(MW of albumin), the sieving of albumin and inflammatory mediators that have a MW between
15 and 50 kDa is minimal because many filtration membranes are hydrophobic and prone to
clogging and cake formation by plasma proteins. For these reasons, currently available dialyzers and hemofilters are useless for performing blood purification in hepatic failure where
large quantities of circulating albumin-bound
and unbound toxins, inflammatory mediators,
and other harmful molecules must be removed.
These observations have prompted the development of blood filtration devices with albuminleaking membranes [79,80]. The concept of selective large-pore hemofiltration, gains further
support from the knowledge of the role of albumin in blood detoxification. In this capacity, albumin inactivates numerous toxins and other ligands through binding and transports them to
the liver for chemical transformation and excretion, or to the kidney for excretion. In hepatic
failure, there is a rapid and significant accumulation of albumin bound toxins, including bile
acids, phenols, bilirubin, mercaptans, dioxin-like
substances, tryptophan, and many other noxious
molecules. When the binding capacity of albumin is exhausted, the effects of circulating toxins and harmful mediators become more pronounced. Accumulation of these components in
the blood may even become life- threatening, affecting not only the liver, but also the brain, kidneys, lungs, and immune system. Additionally,
it was demonstrated that during hepatic failure,
sepsis, and other pathological conditions associated with severe toxemia and systemic inflammation, circulating albumin undergoes structural
and functional modifications that negatively affect its ability to bind toxins [96,97]. In the recent study by Jalan et al. [98], all parameters estimating albumin function (functional capacity
of the binding sites, transport efficiency, and detoxification efficiency) were found to be severely compromised in patients with acute decompensation of cirrhosis.
From the medical standpoint, these data have
2 potential implicatations. First, albumin-binding capacity (ABC) alone or in combination with
other measures of hepatic function may emerge
as a valuable prognostic test in patients with liver failure. Second, hemofiltration using an albumin-leaking membrane may be a simple and
effective method for purifying blood from albumin-bound toxins and restoring normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules
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