Estimation and Application of Biological Variation of Urinary δ-Aminolevulinic Acid and Porphobilinogen in Healthy Individuals and in Patients with Acute Intermittent Porphyria

Abstract

Background: Diagnosis of an attack of acute intermittent porphyria (AIP) is based on the demonstration of increased concentrations of porphobilinogen (PBG) and ␦-aminolevulinic acid (ALA) in urine, but many AIP patients also have high baseline concentrations in remission. The aim of this study was to estimate the biological variations of ALA, PBG, and porphyrins in healthy individuals and AIP patients to improve interpretation of test results. Methods: Fifteen healthy individuals and 15 AIP patients were included, and biological variations were calculated based on urine samples collected weekly for 10 consecutive weeks. For the AIP patients, long-term variations were also estimated based on 7 samples collected through a 2-year period. Results: The porphyrin variances were inhomogeneously distributed; biological variations of porphyrins were therefore not calculated. The within-subject biological variations of ALA and PBG were 16%-20% in the short-term settings and for PBG, 25% in the long-term setting, giving reference change values of ϳ50% and 70%, respectively. The probability of detecting a 100% real change in PBG was 97% in the short-term setting and 80% in the long-term setting. Conclusions: In an AIP patient, a 2-fold increase in PBG, independent of the baseline concentration, will be detected with a probability >80% and is most likely related to the patient's disease and not caused only by

Reference change values to assess changes in concentrations of biomarkers of exposure in individuals participating in a cigarette-switching study

“…This methodology provides reference values based on within-subject (CV I ) and between-subject (CV G ) biological variation and, therefore, enables dissociation between analytical and biological variability. RCVs are widely implemented to help clinicians in the interpretation of laboratory tests intended to monitor subjects over time and/or to assess the prognosis of diseases [34,35]. This methodology enables incorporation of more than two time-points into the analysis to calculate the sources of variability.…”

Discrepancies in International Normalized Ratio Results between Instruments: A Model to Split the Variation into Subcomponents

“…Note that the CV within-person here includes the analytical variance. The ranked variances should follow a 2 distribution, which was tested by Bartlett's test (31 ). Statistical significance was set to Ͻ0.05, which was also illustrated in rankit plots with CV within-person as the abscissa and ranked cumulated fractions as the ordinate.…”

Reference intervals for 24 laboratory parameters determined in 24-hour urine collections

“…These reference intervals are in the same range as those of our study. However, it is worth mentioning that for porphyrin analysis a large inter-laboratory variation has been reported recently [35].…”