Comparison of uncertainties related to standardization of urine samples with volume and creatinine concentration

When measuring biomarkers in urine, volume (and time) or concentration of creatinine are both accepted methods of standardization for diuresis. Both types of standardization contribute uncertainty to the final result. The aim of the present paper was to compare the uncertainty introduced when using the two types of standardization on 24 h samples from healthy individuals. Estimates of uncertainties were based on results from the literature supplemented with data from our own studies. Only the difference in uncertainty related to the two standardization methods was evaluated. It was found that the uncertainty associated with creatinine standardization (19-35%) was higher than the uncertainty related to volume standardization (up to 10%, when not correcting for deviations from 24 h) for 24 h urine samples. However, volume standardization introduced an average bias of 4% due to missed volumes in population studies. When studying a single 24 h sample from one individual, there was a 15-20% risk that the sample was incomplete. In this case a bias of approximately 25% was introduced when using volume standardization, whereas the uncertainty related to creatinine standardization was independent of the completeness of the sample. The uncertainty of creatinine standardization is increased when studying single voids rather than 24 h urine samples. This is partially counteracted by the increased statistical power due to the increased number of samples for each individual. Furthermore, there is a considerable increase in convenience for the participants, when collecting small volumes rather than complete 24 h samples.