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

Figures & data

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

Table 1 Selected normal values for serum albumin, absolute and fractional plasma synthesis rates, and plasma and total body distribution of albumin

Reference	Method	Serum albumin (g/dL)	Absolute synthesis rate (mg/kg/day)	Plasma fractional synthesis rate (%/day)	Total albumin turnover time (day)	Plasma albumin mass (g)	Plasma/total albumin
92	^131I PK	4.18	142	8.9	33	120	0.34
118	^131I PK	3.7	134	8.57	33	101	0.35
118	^131I urinary excretion	3.7	127	7.4	NR	NR	NR
119	^131I PK	4.3	150	8.5	26	126	0.45
120	^131I PK	4.31	185	9.6	25	130	0.42
121	^125I PK	4.63	197	12.8	19	108	0.41
12	^14CO3 precursor	4.5	239	13.4	NA	NR	NA
122	^13C leucine precursor	4.7	157	7.2	NA	154	NA
123	^13C leucine precursor	4.4	146	7.9	NA	143	NA

Note: ¹³¹I PK or ¹²⁵I PK is steady-state tracer kinetics.

Abbreviations: NA, not available by this technique, NR, not reported.

Table 2 Human pathological albumin fractional turnover, absolute synthesis rates, and albumin plasma and total body distribution

Reference	Method	Serum albumin (fraction normal)	Absolute synthesis (fraction normal)	Plasma fractional synthesis (fraction normal)	Total albumin turnover time (fraction normal)	Plasma albumin mass (fraction normal)	Plasma/total albumin (fraction normal)	Comments
Liver disease
131	^131I PK	0.68	0.78	NR	1.21	NR	NR
118	^131I PK	0.84	0.7	0.69	1.28	1.08	1.13	No diuretics
		0.88	0.68	0.75	1.26	1.01	1.13	Diuretics
120	^131I PK	0.62	0.56	0.72	1.47	0.7	0.87
123	^13C leucine	0.84	0.81	1.0	NA	NR	NA	Mild disease
132	^2H phenylalanine	0.79	0.7	0.76	NA	0.75	NA	Child–Pugh A
		0.51	0.34	0.44	NA	0.73	NA	Child–Pugh B
		2.23	0.25	0.57	NA	0.53	NA	Child–Pugh C
133	^14CO3 precursor	0.8	0.66	0.68	NA	0.71	NA	Acute hepatitis
		0.83	1.02	0.97	NA	0.75	NA	After recovery
134	^14CO3 precursor	0.63	0.59	0.72	NA	0.66	NA	Before treatment
		0.67	1.13	1.34	NA	0.67	NA	13 day course prednisolone
Kwashiorkor, 1- to 2-year-old infants, ratio of before/after nutritional treatment
24	^125I urine and fecal	0.65	0.43	NA	NA	NA	NA
25	excretion	0.75	0.73	NA	NA	NA	NA
Rheumatoid arthritis
135	^14CO3	0.65	0.83	0.86	NA	0.65	NA
Chronic congestive heart failure and weight loss
136	^14CO3	0.69	0.91	1.57	NA	NR	NA
Chronic renal failure
137	^14CO3 precursor	0.88	0.99	0.89	NA	1.1	NA
121	^125I PK	0.80	1.03	0.91	0.97	1.09	1.16	Continuous peritoneal dialysis
Chronic renal failure: comparison of patients with upper and lower quartile CP
41	^125I PK	0.91	1.0	1.0	NR	1.0	1.0	Upper CP
		0.7	0.79	1.0	NR	0.7	1.0	Lower CP
Chronic renal failure: individual sequential measurements before and after fall of CP from normal value
40	^125I PK	1.0	1.0	1.0	NR	1.0	1.0	Normal CP
		0.88	0.84	1.0	NR	0.84	1.0	After fall
Hypertension
37	^131I PK	1.03	1.54	1.71	0.59	0.89	1.02
Acromegaly, increased growth hormone
38	^131I PK	1.0	1.63	1.6	0.68	1.0	0.93
Inflammatory disease (4 patients: pyelocystitis, abscess, endocarditis, pulmonary embolism
138	^14CO3	0.61	0.75	1.03	NA	0.62	NA
Cachetic cancer patients with acute-phase protein response
139	[^2H5]-phenylalanine	0.76	1.08	1.35	NA	0.66	NA
Severe head trauma
140	^13C leucine	0.82	1.46	1.56	NA	NR	NA
Critically ill ICU patients
141	[^2H5]-phenylalanine	0.7	2.24	2.75	NA	NR	NA	Misc, sepsis, bleeding, shock, etc
Albumin synthesis during laparoscopic cholecystectomy: cholecystitis vs elective surgery
142	[^2H5]-phenylalanine	0.8	1.31	1.44	NA	NA	NA	Cholecystitis
Wiskott–Aldrich syndrome
42	^131I PK	0.93	2.06	1.9	0.52	2.0	1.0	5 children
Nephrotic syndrome adults
56	^131I PK	0.38	1.21	3.1	0.28	0.38	1.22
57	^125I PK	0.42	1.2	3.09	0.27	0.55	1.21	High protein diet
		0.41	0.89	2.13	0.4	0.46	1.31	Low protein diet
143	^13C leucine	0.66	1.47	2.32	NA	0.61	NA
Protein-losing enteropathy
61	^131I PK	0.67	1.56	NR	0.56	0.9	1.04	Regional enteritis and ulcerative colitis
12	^14CO3 precursor	0.63	2.66	3.27	NA	0.60	NA	Miscellaneous
64	^14CO3 precursor	0.5	1.42	3.0	NA	0.52	NA	Intestinal lymphangiectasia

Notes: All the results are presented as the fraction of the reported normal control values. ¹³¹I PK and ¹²⁵I PK, pharmacokinteic study using tracer ¹³¹I or 125I labeled albumin.

Abbreviations: C_P, serum albumin concentration; misc, miscellaneous; NA, not available by this technique, NR, not reported.

Table 3 Acute changes in albumin synthesis rates in normal human subjects

Reference	Method	Serum albumin (fraction control)	Absolute synthesis (fraction control)	Plasma fractional synthesis (fraction control)	Comments
Low-protein, isocaloric diet
124	^2N glycine precursor	1.0	0.75	0.75	14 days, 28 g protein/day
125	^131I PK	0.63	0.8	0.59	4 weeks, 10 g protein/day
126	^125I PK	0.9	0.35	0.6	5 weeks, 10 g protein day
Postabsorptive vs fasting basal
127	^2C leucine	NR	1.46	NR	Normal subjects
		NR	1.03	NR	Cirrhotic subjects
17	^2C leucine	NR	1.9	1.92
128	[^2H5]-phenylalanine	NR	1.2	1.22	Young subjects
129	[^2H5]-phenylalanine	NR	1.32	NR
12 hours IV infusion nutrient solution mixture (106 g amino acids)
18	[^2H5]-phenylalanine	NR	NR	1.07
Insulin withdrawal in type I diabetics
130	^2C leucine	1.0	NR	0.7	Insulin withdrawal
Metabolic acidosis (7 days, 4.2 mmol NH4Cl/kg/day ingestion)
19	[^2H5]-phenylalanine	0.97	NR	0.81	Serum pH =7.303
2 hours following IV endotoxin
22	[^2H5]-phenylalanine	0.95	NR	1.39
6 hours infusion of stress hormones (epinephrine, cortisol, and glucagon)
21	[^2H5]-phenylalanine	NR	NR	1.02	At 6 hours
		NR	NR	1.17	At 18 hours

Note: Values are expressed relative to control.

Abbreviations: IV, intravenous; NR, not reported.

Figure 2 Plot of albumin synthesis versus serum albumin (both normalized to the normal values) for subjects with acute and chronic liver disease.

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 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 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 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 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 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 S1 Schematic diagram of the two different compartmental models.

Notes: I(t): input to system as function of time t; M_i(t): amount of solute in compartment i; k_i: rate constant for excretion from compartment i; k_ij: rate constant for exchange from compartment i to compartment j; Q: amount of excretion.

FulksMStoutRLDolanVFAlbumin and all-cause mortality risk in insurance applicantsJ Insur Med2010421111721290995

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