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Cited by 764Clinical Nutrition and GastroenterologyProtein Interaction Studies and Fluorescence AnalysisLiver Disease and Transplantation

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Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements

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Levitt, David, Levitt, Michael·2016·International Journal of General Medicine
DOI 10.2147/ijgm.s102819PMC PMC4956071
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Abstract

Serum albumin concentration (CP) is a remarkably strong prognostic indicator of morbidity and mortality in both sick and seemingly healthy subjects. Surprisingly, the specifics of the pathophysiology underlying the relationship between CP and ill-health are poorly understood. This review provides a summary that is not previously available in the literature, concerning how synthesis, catabolism, and renal and gastrointestinal clearance of albumin interact to bring about albumin homeostasis, with a focus on the clinical factors that influence this homeostasis. In normal humans, the albumin turnover time of about 25 days reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal (≈6%), gastrointestinal (≈10%), and catabolic (≈84%) clearances. The acute development of hypoalbuminemia with sepsis or trauma results from increased albumin capillary permeability leading to redistribution of albumin from the vascular to interstitial space. The best understood mechanism of chronic hypoalbuminemia is the decreased albumin synthesis observed in liver disease. Decreased albumin production also accounts for hypoalbuminemia observed with a low-protein and normal caloric diet. However, a calorie- and protein-deficient diet does not reduce albumin synthesis and is not associated with hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease states other than liver disease, albumin synthesis is normal or increased, and hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either from an increased rate of catabolism (a poorly understood phenomenon) or enhanced loss of albumin into the urine (nephrosis) or intestine (protein-losing enteropathy). The latter may occur with subtle intestinal pathology and hence may be more prevalent than commonly appreciated. Clinically, reduced CP appears to be a result rather than a cause of ill-health, and therapy designed to increase CP has limited benefit. The ubiquitous occurrence of hypoalbuminemia in disease states limits the diagnostic utility of the CP measurement.

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Crossref · 10.2147/ijgm.s102819

Cites

158 of 158 references verified0 citation errors · 0 not checkable

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Figures

Figure 1 Relationship of serum albumin concentration to relative risk of mortality for 50- to 69-year-old male life insurance applicants. Notes: The dashed line indicates a relative risk of 1.0. The means and 95% confidence limits of relative mortality (medium follow-up of 12 years) are shown for groups of subjects with the mean serum albumin concentrations listed. Adapted from Fulks M, Stout RL, Dolan VF. Albumin and all-cause mortality risk in insurance applicants. J Insur Med. 2010;42(1):11–17. Copyright © 2010 Journal of Insurance Medicine.4
Figure 1 Relationship of serum albumin concentration to relative risk of mortality for 50- to 69-year-old male life insurance applicants. Notes: The dashed line indicates a relative risk of 1.0. The means and 95% confidence limits of relative mortality (medium follow-up of 12 years) are shown for groups of subjects with the mean serum albumin concentrations listed. Adapted from Fulks M, Stout RL, Dolan VF. Albumin and all-cause mortality risk in insurance applicants. J Insur Med. 2010;42(1):11–17. Copyright © 2010 Journal of Insurance Medicine.4CC BY-NC · PubMed Central
Figure 2 Plot of albumin synthesis versus serum albumin (both normalized to the normal values) for subjects with acute and chronic liver disease.
Figure 2 Plot of albumin synthesis versus serum albumin (both normalized to the normal values) for subjects with acute and chronic liver disease.CC BY-NC · PubMed Central
Figure 3 Plot of the clearance of antipyrine (black), indocyanine green (red), or aminopyrine (blue) versus serum albumin (normalized to the normal value). Notes: The solid line is the expected relationship if clearance is proportional to serum albumin. Data from references 33–36.
Figure 3 Plot of the clearance of antipyrine (black), indocyanine green (red), or aminopyrine (blue) versus serum albumin (normalized to the normal value). Notes: The solid line is the expected relationship if clearance is proportional to serum albumin. Data from references 33–36.CC BY-NC · PubMed Central
Figure 4 Plot of either the total albumin synthesis rate relative to normal (red) or the urinary albumin excretion relative to total synthesis (black) versus the urinary albumin excretion in a series of nephrotic syndrome patients with varied diagnoses and no obvious liver disease. Note: Experimental data from references 56 and 57.
Figure 4 Plot of either the total albumin synthesis rate relative to normal (red) or the urinary albumin excretion relative to total synthesis (black) versus the urinary albumin excretion in a series of nephrotic syndrome patients with varied diagnoses and no obvious liver disease. Note: Experimental data from references 56 and 57.CC BY-NC · PubMed Central
Figure 5 Plot of either the total albumin synthesis rate relative to normal (red) or the urinary albumin excretion relative to total synthesis (black) versus the serum albumin relative to normal. Note: Experimental data from references 56 and 57.
Figure 5 Plot of either the total albumin synthesis rate relative to normal (red) or the urinary albumin excretion relative to total synthesis (black) versus the serum albumin relative to normal. Note: Experimental data from references 56 and 57.CC BY-NC · PubMed Central
Figure 6 Plot of serum albumin versus the percent of an intravenous dose of 51Cr-labelled albumin collected over 4 days of stool sampling in 50 control subjects and 130 patients with hypoalbuminemia and no obvious liver or renal disease. Note: Experimental data from reference 63.
Figure 6 Plot of serum albumin versus the percent of an intravenous dose of 51Cr-labelled albumin collected over 4 days of stool sampling in 50 control subjects and 130 patients with hypoalbuminemia and no obvious liver or renal disease. Note: Experimental data from reference 63.CC BY-NC · PubMed Central
Figure 7 Plot of the percent of plasma albumin that is synthesized/day versus the percent of plasma albumin that is excreted into the GI tract/day in subjects with increased GI albumin clearance and hypoalbuminemia. Note: Experimental data from reference 63. Abbreviation: GI, gastrointestinal.
Figure 7 Plot of the percent of plasma albumin that is synthesized/day versus the percent of plasma albumin that is excreted into the GI tract/day in subjects with increased GI albumin clearance and hypoalbuminemia. Note: Experimental data from reference 63. Abbreviation: GI, gastrointestinal.CC BY-NC · PubMed Central
Figure 8 Distribution of all serum albumin concentrations measured in a single day at the Minneapolis Veterans Administration Hospital for outpatients and inpatients. Note: The heavy dashed line is the lower limit of normal (lowest 2.5% of values) and the short dashed line is the average value observed in a group of 50- to 69-year-old life insurance applicants.
Figure 8 Distribution of all serum albumin concentrations measured in a single day at the Minneapolis Veterans Administration Hospital for outpatients and inpatients. Note: The heavy dashed line is the lower limit of normal (lowest 2.5% of values) and the short dashed line is the average value observed in a group of 50- to 69-year-old life insurance applicants.CC BY-NC · PubMed Central

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Cites

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Research works printed but not linked: 3

  1. [16]Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients): A Report of the Panel on Macronutrients, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Washington, DC National Academies Press 2005
  2. [92]Takeda Y Reeve EB Studies of the metabolism and distribution of albumin with autologous I131-albumin in healthy men J Lab Clin Med 1963 61 183 202 13984638
  3. [122]Ballmer PE McNurlan MA Milne E Measurement of albumin synthesis in humans: a new approach employing stable isotopes Am J Physiol 1990 259 6 Pt 1 E797 E803 2260648

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Metadata

Authors
Levitt, D., & Levitt, M.
Affiliations
  • University of Minnesota (US)
  • Veterans Health Administration (US)
Corresponding author
Levitt, Michael
ORCID
Venue
International Journal of General Medicine
Publisher
Informa UK Limited
Published
2016-07
Volume
Volume 9
Pages
229-255
ISSN
1178-7074 (ISSN-L)
DOI
10.2147/ijgm.s102819
PMC
PMC4956071
OpenAlex
W2488911476
Cited by
763
References
156
Citations by year
2026: 97 · 2025: 91 · 2024: 88 · 2023: 101 · 2022: 96 · 2021: 117 · 2020: 73 · 2019: 49 · 2018: 27 · 2017: 20 · 2016: 3
FWCI
34.47
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of General Medicine (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
human serum albumin, hypoalbuminemia, albumin synthesis, albumin catabolism, albumin turnover, protein-losing enteropathy, nephrotic syndrome, liver disease, malnutrition, prognostic factors

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