Invited commentary: evaluation of measures of urinary albumin excretion in epidemiologic studies.

In the current issue of the Journal, Gansevoort et al. (1) raise concerns about our paper (2) that compared the strengths and weaknesses of the urinary albumin concentration and the albumin:creatinine ratio as alternatives to the ‘‘gold standard’’ 24-hour urinary albumin excretion in the International Study of Macronutrients and Blood Pressure (INTERMAP). In that report, which used albumin excretion measures from two 24-hour urine collections, we found that 1) the median within-person coefficient of variation ranged from 25.3 to 81.3 percent for the three measures, with the albumin concentration generally having slightly smaller withinperson coefficients of variation; 2) the albumin:creatinine ratio had larger rank-order correlations with 24-hour excretion than did the urinary albumin concentration (0.949 for men and 0.942 for women vs. 0.881 and 0.816 for the albumin concentration); and 3) the average correlations with blood pressure were similar for the three measures, but the correlation with body mass index was lower for the albumin: creatinine ratio (0.118 vs. 0.188 for the albumin concentration and 0.211 for 24-hour excretion), because of high correlation between body mass index and the creatinine level. On the basis of these findings and the lower costs associated with the albumin concentration, we concluded that both the albumin concentration and the albumin:creatinine ratio appeared to be reasonable alternatives to 24-hour albumin excretion for epidemiologic studies. We also suggested that the albumin concentration was the better alternative to 24-hour excretion for studies in which measures of body size and obesity were key variables or the cost of creatinine measurement was an important consideration. When these concerns did not apply, we suggested that the albumin:creatinine ratio was the better alternative to 24-hour excretion. Gansevoort et al. indicate that, for INTERMAP, ‘‘the coefficients of variation for all the variables are so high that they in fact disqualify the use of urinary albumin measures as a reliable risk marker for future cardiovascular events’’ (1, p. 726). Their statement suggests that the within-person coefficient of variation determines whether or not a variable is reliable. However, the within-person coefficient of variation is but one measure that can be used to assess the reliability/reproducibility of a measurement. The generally accepted measure is the intraclass correlation (3). However, the intraclass correlation is typically not suitable for use with albumin excretion measures, because of their highly skewed distributions in most studies, including INTERMAP (2). In addition, most studies on the reproducibility of albumin excretion have used the within-person coefficient of variation (4–7). Hence, for INTERMAP, we reported the mean and median within-person coefficient of variation, as well as the Spearman rank-order correlation between the first and repeat measurements of each albumin measure as an alternative to the intraclass correlation. In the total sample, rank-order correlations for the three albumin measures ranged from 0.624 to 0.658 in men and from 0.562 to 0.609 in women. These values were larger than those for urinary urea, which had rank-order correlations of 0.593 in men and 0.553 in women, although the median within-person coefficients of variation for urinary urea were 12.5 percent in both men and women, that is, values approximately 75 percent smaller than those for the albumin measures.