The amount of urinary albumin or protein is an important diagnostic and prognostic factor in patients with kidney disease (Peterson et al., 1995; Bigazzi et al., 1998; Leehey et al., 2005). Many trainees are uncertain about how to interpret the urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR). Possibly, some of this confusion can be blamed on the nephrology community, as literature and guidelines sometimes incorporate one measurement, sometimes the other, and sometimes both. Laboratories also vary in their testing practices, with some not measuring UACR if there is overt (i.e., dipstick-positive) proteinuria. This practice stems from the fact that in the past urinary albumin measurement was generally done by immunoassay, which was more laborious and expensive than urinary total protein measurement. With current autoanalyzers, however, it is usually very simple and inexpensive to run and report both UACR and UPCR on the same specimen. We generally use both UACR and UPCR in the initial evaluation of the patient with proteinuria. In those with established proteinuric kidney disease, we typically follow just the UPCR.

First, let us review some concepts. Most proteins, that is, albumin and globulins, are too big to pass through the normal glomerular filtration barrier in substantial amounts, and thus persistent proteinuria is usually a sign that the glomeruli are damaged. Glomerular proteinuria can be transient if it results from increased hydrostatic pressure (such as in congestive heart failure) or variables such as exercise or fever. It is pathologic only if the proteinuria is persistent. There are other smaller
molecular weight proteins in the plasma that are filtered and normally reabsorbed by the renal tubules, including light chains (polyclonal), alpha-1-microglobulin, and beta-2-microglobulin. Impaired tubular reabsorption of these filtered proteins indicates tubular damage (“tubular proteinuria”). Finally, “overflow proteinuria” occurs in situations in which abnormally large concentrations of small proteins (such as monoclonal light chains, hemoglobin, or myoglobin) are produced and are freely filtered by the glomerulus, overwhelming the capacity of the renal tubules to completely reabsorb and catabolize these proteins, so they appear in the urine. Typically, overflow proteinuria is due to the overproduction of monoclonal proteins, sometimes called “paraproteins.”