Comparison of Different Methods of Urinary Protein Excretion Measurement: Is the King Really Dead?

Assessing proteinuria is of uttermost importance for a nephrologist. It is often indispensable to accurately quantify the amount of protein lost, hence complicated and time-consuming urine collections (the gold standard or "king" of methods - 24-h protein excretion rate [PER]) are often replaced by spot urinary protein to creatinine ratio (PCR). The aim of the study was to determine whether the latter can reliably compare to the gold standard and whether "timing" of a spot urine sample is essential.

We performed a prospective, single-center study of 143 consecutive adult patients with glomerular proteinuria (a total of 187 cases). Protein and creatinine concentration was measured in 3 consecutive urine samples (starting with the first morning void) and a simultaneous 24-h urine collection. Agreement between 24-h PER and PCR was evaluated with Bland-Altman plots.

Compared to PER 3 consecutive PCRs were 0.86, 0.66, and 0.50 higher with wide limits of agreement respectively. The bias between 2 methods was influenced by sex, CKD stage, albumin concentration and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. In 24 participants, in whom at least 2 measurements at different time points were available, only 88% of differences were lower than the calculated repeatability coefficient.

Unfortunately although random PCR correlates with 24-h protein excretion, the scatter of differences increases as 24-h proteinuria rises (without any significant effect of the sampling time). The observed lack of agreement makes PCR an unsuitable parameter to correctly quantify proteinuria; it is also not useful for monitoring the amount of daily proteinuria in the same patient. Therefore, while searching for new markers, nephrologists can only say: "long live the king!"