Monitoring Urinary Orosomucoid in Acute Inflammation: Observations on Urinary Excretion of Orosomucoid, Albumin, α1-Microglobulin, and IgG

Abstract

Background: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (␣ 1 -acid glycoprotein), albumin, ␣ 1 -microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. Methods: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgeryinduced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. Results: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for ␣ 1 -microglobulin, 33-fold for albumin, and 26-fold for IgG. Conclusions: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically rele-

Coelution of Other Proteins with Albumin during Size-Exclusion HPLC: Implications for Analysis of Urinary Albumin

“…The aggregate concentration in plasma of globulins with a molecular size similar to albumin, proteins such as transferrin, ␣ 1 -acid glycoprotein, ␣ 1 -proteinase inhibitor, ␣ 1 -antichymotrypsin, ␣ 2 -HS glycoprotein, hemopexin, Gc-globulin, and many others (31 ), in healthy individuals is ϳ25% that of albumin; this aggregate concentration is even higher during acutephase reactions (32 ). Because the passage of plasma proteins through the glomerular barrier into urine is primarily a size-dependent process with a size-exclusion limit approximately the size of albumin (33 ), it is not surprising that all of the albumin-sized plasma components are also found in urine (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(33)(34)(35)(36)(37)(38)(39). There is considerable variation in the reported proportions of individual globulins relative to albumin in urine (Table 3).…”

“…During acute-phase responses, for example, the urinary concentration of ␣ 1 -acid glycoprotein reaches ϳ80% that of albumin (24 ). A second problem with the size-exclusion HPLC analysis is that several urinary components, although not exactly coeluting with albumin, overlap considerably.…”

“…A second problem with the size-exclusion HPLC analysis is that several urinary components, although not exactly coeluting with albumin, overlap considerably. As listed in Table 3, the total concentrations of these components, such as IgG, immunoglobulin light chains, and ␣ 1 -microglobulin, could approach or exceed the albumin concentration (21,24,37,40,41 ). By virtue of its much larger size than albumin, IgG would be expected to be well resolved from albumin; however, under the standard conditions of size-exclusion HPLC analysis, it eluted much later than expected, probably because of adsorption on the column.…”

“…Although albumin is the most abundant plasma protein, there are many other plasma proteins of approximately the same molecular size, such as transferrin, ␣ 1 -proteinase inhibitor, hemopexin, ␣ 1 -acid glycoprotein, ␣ 1 -antichymotrypsin, Gc-globulin, ␣ 2 -HS glycoprotein, and transthyretin, that are major urinary components (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Fundamental principles suggest that size-exclusion HPLC will not resolve albumin from other urinary proteins of similar molecular size.…”

Urinary orosomucoid: validation of an automated immune turbidimetric test and its possible clinical use

“…Previously we showed that u-ORM could be a more sensitive marker of inflammation than serum ORM which rises only 2-fold in contrast to even 200-fold increase of u-ORM in sepsis ( 21 ). Others also showed that the elevation of u-ORM is much more considerable than that of serum ORM in relation to inflammatory diseases ( 10 , 11 , 17 ). These results indicate that u-ORM is a reliable marker of chronic and acute inflammatory disorders and provides valuable supplementary information for daily clinical practice.…”