Abstract:
Urinary creatinine and dissolved solids concentrations are used in the field of environmental exposure monitoring. This dissertation focuses on the following studies: 1) changes in urinary creatinine or dissolved solids concentrations over sample storage time or condition; 2) percent of younger age groups that fall outside of the World Health Organization (WHO) guideline ranges for valid urine samples using urinary creatinine and dissolved solids concentrations; 3) effect of personal factors on urinary creatinine and dissolved solids concentration and excretion rate; 4) effect of personal factors on different methods of expressing urinary riboflavin (a surrogate xenobiotic) results; and 5) ability of urinary creatinine or dissolved solids concentration to adjust urinary riboflavin concentrations for different states of hydration.
Chapter 3 describes the urinary creatinine and dissolved solids sample stability investigation. We found no trend over sample storage time or condition. However, we did find that repeated analyses on the same urine sample yielded creatinine and dissolved solids concentrations with high coefficients of variation. The variability could impact the apparent xenobiotic result when its concentration is normalized with either urinary creatinine or dissolved solids concentration.
Chapter 4 compared urinary creatinine concentrations in young children and adults from three University of Washington data sets to the WHO guideline ranges. When sample results fall outside of these ranges, the sample is considered invalid and collection of another urine void is recommended. Results showed up to thirty percent of young children had urinary creatinine concentrations that, according to WHO, are too dilute for valid sample analysis. This same population had no samples that were considered too concentrated. In the adult data set, from one to two percent of samples fell either above or below the guideline values. This suggests that separate guidelines are necessary for children. Chapter 5 conducts the same comparisons for dissolved solids concentrations. Results are similar.
Chapter 5 also explores the effect of personal factors on urinary creatinine and dissolved solids concentrations. Factors known to influence urinary creatinine and dissolved solids concentrations include muscle mass, age, gender, and renal function. Urinary creatinine concentration, in particular, is influenced by muscle mass, as it is a byproduct of muscle metabolism. Research conducted as a part of this dissertation and by others has shown differences in urinary creatinine and dissolved solids concentrations with age and gender. This lead to developing age- and gender-specific reference range guidelines for use in determining sample validity. Chapter 5 findings indicate that creatinine concentrations are more highly associated with height and body surface area (BSA) than age or gender. Therefore, developing height- or BSA-specific urinary creatinine concentration guidelines may be more accurate.
Chapter 6 focuses on the ultimate goals of this dissertation. The approach involved administration of a known dose of riboflavin (a surrogate xenobiotic) to participants from 2 up to 31 years of age. Participants provided timed, discrete, total void samples for 24-hours after riboflavin was ingested. The first goal was to determine which personal characteristics most affected the different means of expressing urinary riboflavin results. Participant height was most associated with each method of expression. Urinary riboflavin concentration normalized with creatinine concentration had the highest association with height. Urinary riboflavin concentration normalized with dissolved solids concentration had no association with any of the personal factors tested.
All participants received the same dose of riboflavin (mg/kg body weight). It was found that when urinary riboflavin was normalized using urinary creatinine or dissolved solids resulted in higher values for young children compared to adults. Therefore, when interpreting urinary xenobiotic results, children may appear to be more exposed than adults. When urinary riboflavin was expressed as excretion rate, the opposite was true. Children had lower urinary riboflavin excretion rats than adults.
The final goal was determining if normalizing the urinary xenobiotic concentration with cretinine or dissolving solids truly adjusts for difference in sates of hydration (urine flow rate). Results show that normalizing urinary riboflavin concentration with dissolved solids concentration or, to a lesser extent, does adjust for differences in urine flow rate within individuals. The same is somewhat true for between-individual comparisons, but perhaps not enough to allow comparing results of one individual to another.