Proteinuria without albuminuria: Urinary protein excretion by a subset of patients with burn injuries

Background: There is disagreement regarding the utility of urinary albumin excretion as a marker for capillary injury in patients with severe burn injuries. We examined protein components in urine specimens from patients with burn injury. Methods: Detailed analysis was performed for a set of 5 urine specimens selected based on a high ratio of albumin-sized molecules by size-exclusion HPLC (AccuminR) versus albumin by immunoassay methods. Specimens were analyzed for total protein, α1-microglobulin, α1-acid glycoprotein, cystatin C, and retinol-binding protein. Urine components were analyzed by chromatographic and electrophoretic methods. Major components were identified by mass spectrometry of tryptic peptides. Results: A subset of urine specimens had increased total protein with slight increases in albumin by immunoassay or by polyacrylamide gel electrophoresis. Albumin values by size-exclusion HPLC were more than 10-fold higher. Immunoassays for α1-microglobulin and α1-acid glycoprotein yielded concentrations 5-10 fold higher than for albumin. Other major components identified included zinc-α2-glycoprotein and leucine-rich-α2-glycoprotein. Conclusions: A subset of patients with burn injury had increased total urinary protein resulting primarily from increased excretion of proteins such as α1-microglobulin and α1-acid glycoprotein with little increase in albumin excretion. The unusual composition of urinary proteins in these patients may relate to decreased filtered load of albumin and increased filtered load of acute phase reactants or to alterations in renal tubular protein processing. Thus, measurement of urinary albumin may have decreased sensitivity for detecting kidney injury in burn patients.