How Should We Measure the Albumin in Urine

Laboratories almost universally use immunochemical methods to detect microalbuminuria, defined variously as an albumin excretion of 30–300 mg/day, an albumin/creatinine ratio of 30–300 mg/g, or an albumin excretion rate of 20–200 μg/min. (The term microalbuminuria is a misnomer, of course. No small form of albumin exists that is comparable, for example, to β2-microglobulin, but the term now seems too deeply imbedded in the diabetic literature to be replaced.) During the last 3 years, size-exclusion HPLC has been promoted to detect forms of albumin that are not reactive immunochemically (1)(2). The authors of these studies claimed that this approach is more sensitive in detecting increases in urinary albumin and detects them earlier than do the immunochemical methods (3). They isolated this nonimmunoreactive albumin form after adsorption on immobilized anti-albumin and found that it contained <1% of the potential contaminants transferrin, α1-acid glycoprotein, and α1-antitrypsin by immunochemical tests and little, if any, by mass spectrometry. A challenge to …