Abstract
Albuminuria (mainly in the field of so-called microalbuminuria) is regarded as the most important predictor of high risk for the development of diabetic nephropathy. In addition to predicting nephropathy, microalbuminuria is also a marker of increased risk of cardiovascular diseases and risk factor for all-cause mortality.
The terms "microalbuminuria", "normoalbuminuria" and "macroalbuminuria" should be discontinued, and replaced with the term "urine albumin". The terms cause confusion, and uninitiated interpreters often wonder if there is a small, ordinary or large albumin molecule being excreted.
The concentration of albumin excreted in 24 h was used in the past. The difficulty collecting 24 h urine samples has lead to the common recommendation to use an untimed urine collection and to report the ratio of the albumin concentration to the creatinine concentration.
This albumin/creatinine ratio (ACR, in units of mg/mmol, mg/g) is widely viewed as an acceptable surrogate for albumin excretion rate. First morning void urine samples provide lower variability than random samples.
Intact albumin in urine may exist in two forms, immunoreactive and immunounreactive. Previous estimates of albuminuria have only detected immunoreactive forms.
Urinary albumin is traditionally measured using immunochemical methods such as immunoturbidimetry, immunonephelometry, radioimmunoassay, enzyme immunoassay. High-performance liquid chromatography (HPLC) probably detects additional albumin that is missed by immunochemical methods.
Comparison of albumin/creatinine ratio by HPLC with immunochemical methods showed positive proportional bias, which decreased with increasing concentrations of albumin. Some studies have even demonstrated that the HPLC method can identify those with albuminuria approximately 2 to 4 years earlier than current methodology, and thus it identifies some people at increased risk of morbidity and mortality.
Recently, several proteins (for example transferrin, ?-1-acid glycoprotein, ?-1-proteinase inhibitor) were found to be coeluted along with albumin during HPLC analysis. In this case HPLC could possibly provide falsely higher results.
This implies that differences between HPLC and immunochemical methods are interpreted either as lowered immunoreactivity of urine albumin, or as nonspecificity of HPLC method for assessment urine albumin. These controversial findings are thus becoming the starting-point for our research.