Weekly Biological Variability of Urinary Organic Acids

Abstract

Use of LC-MS/MS methods has improved sample preparation and increased throughput for the measurement of 40 or more organic acids in urine. In order to assess the significance of abnormalities that might be attributed to nutritional inadequacies or other metabolic disturbances, the week-to-week variation of results due to normal physiological responses needs to be established. This study determined the biological variability for 37 organic acids plus hippuric acid, D-arabinitol and 8-hydroxy-2'deoxyguanosine in overnight urine specimens from eight weekly samples submitted by 22 healthy adults. For the 40 analytes, CV b values varied from 12.3 to 74.3. Fourteen of the analytes had CV b values less than 30 and another 19 of them were less than 50. Multiple analytes displayed the property of increasing variability with concentration that may be characteristic of most intermediary metabolites. Linear regression line slopes for CV b vs. concentration were tabulated to assist the use of this information. The 40 analytes display biological variability in the range of disease risk markers such as serum lipoprotein cholesterol concentrations, cancer markers and thyroid hormones. The likelihood of a single measurement being representative of the true mean concentration varies with the analyte and the level found. Data reported here demonstrate reliability of results of urinary organic acid profiling performed under the reported analytical conditions. [N A J Med Sci. 2012;5(3): 148-156.]

Long-term patterns of urinary pyroglutamic acid in healthy humans

“…Pyroglutamic acid (PGA or 5‐oxoproline) was measured in urine specimens submitted once weekly for 8 weeks by 22 subjects as part of an IRB‐approved study to determine biological variability in a profile of organic acids (Lord et al. ). The between‐run analytical variability for pyroglutamate was 3.5% at 50.9 μg/g creatinine, a value anomalously different from its calculated overall biological variability (CV b ) of 33.5%, indicating that something other than analytical variability was contributing to the observed patterns.…”

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

“…Indeed, we observed that cord serum and placental 3-OHB were positively associated with cord serum and placental 2-hydroxybutyrate (2-OHB) and 2-aminobutyrate, biomarkers of glutathione synthesis and status. 42,43 Cord serum 3-OHB was also negatively associated with pyroglutamate, a metabolite related to glutathione depletion 44,45 and positively associated with placental glutathione concentrations. 3-OHB acts as a signaling molecule to protect against oxidative stress through several proposed mechanisms, including activation of antioxidant response-related transcription factors.…”

Maternal Serum and Placental Metabolomes in Association with Prenatal Phthalate Exposure and Neurodevelopmental Outcomes in the MARBLES Cohort

“…Under conditions of oxidative stress, glutathione biosynthesis increases, and cysteine may become limiting. Thus, as a by-product of cysteine production through glutamate-cysteine ligase, 2-hydroxybutyrate is a sign of glutathione synthesis and oxidative stress [85]. DEHP has been shown to reduce glutathione concentrations in mouse kidneys through the depletion of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and glutamate-cysteine ligase abundance [86].…”