Creatinine correction

Fig. 14.1 95th percentile of urine concentrations (pg/g creatinine corrected) for the US population aged 20-59 years, three NHANES surveys. Shaded blocks show 4-nitrophenol (methyl parathion) unshaded blocks show 3,5,6-tnchloro. v-pyndinol... 

A report entitled Chemical Trespass was issued in May 2004 by the Pesticide Action Network (Schafer et al., 2006). It contained detailed analysis of 2000/01 National Health and Nutrition Examination Survey (NHANES) OP urinary metabolite data and used published methods to estimate exposure levels to parent compounds from creatinine corrected urinary metabolite levels. They focused on chlorpyrifos and its metabolite 3,4,6-trichloro-2-pyridinol (TCP), and found that chlorpyrifos exposures for children ages 6-11 and 12-19 exceeded EPA s chronic population-adjusted dose (cPAD) by surprisingly wide margins. Geometric mean TCP levels were 3 to 4.6 times higher than the EPA-estimated safe dose, as shown in Fig. 14.2. The more heavily exposed children received daily doses more than ten times the safe level. 

Mean Urinary DEP Concentration (Creatinine Corrected mg/ml) Observed with the Different Clothing Modalities Worn by Citrus Grove Workers Occupationally Exposed to Ethion, Orange County,... 

It should be noted that for urinary excretion studies the preferred design is to collect 24 h urine. In some special designs it can be argued that the use of spot urine samples and correction for urinary creatinine concentration may be a valid measure. A prerequisite for the spot urine - creatinine correction design is a solid argumentation that creatinine excretion is unchanged by the experimental condition or that it is not different between groups. A theoretical example is comparison of lean men versus fat females. Their cell number is comparable but muscle mass very different. Creatinine excretion is mainly... 

Creatinine in urine. The assay of creatinine in body fluids is one of the core assays in clinical chemistry since its level in blood and urine reflects the functional status of the kidney. There are many methods for its assay ranging from the simple colorimetric Jafle reaction to dedicated creatinine analysers using discrete sampling technologies. For many metabolic assays, the so-called creatinine correction can be applied since creatinine excretion is considered to be constant throughout the day. The clinic therefore only needs to collect a random specimen of urine rather than a full 24 h specimen. 

In another study investigating the dose-effect and dose-response relationship between the Cd concentration in rice and urinary concentrations/prevalence of abnormal levels of markers of renal dysfunction, significant correlations between Cd concentration in rice and concentrations as well as prevalence rates of abnormal urinary p2-microglobulin, metallothionein, glucose and amino-nitrogen levels were found. The highest maximum allowable concentration of Cd in rice calculated for these indicators was 0.34 mg/kg when the uncorrected urinary value was used and 0.29 mg/kg when the creatinine corrected value was used. Both values are lower than 0.4 mg/kg, the tentative limit prescribed by the Japanese government [103]. 

Calculated Clearance. The mathematical relationship between plasma creatinine and GFR can be improved by correcting for the confounding variables that make that relationship nordinear. More than 25 different formulas have been derived that estimate GFR using plasma creatinine corrected for some or all of gender, body size, race, and age. These may produce a better estimate of GFR than serum creatinine alone. Indeed the National Kidney Foundation of the United States has recommended that such estimates should be used in preference to serum creatinine, and that either the Cockcroft and Gault or Modification of Diet in Renal Disease (MDRD) formula should be used in adults. The Schwartz and Counahan-Barratt formulas are recommended for use in children. 

Mage, D. T., Allen, R. H., Gondy, G., Smith, W., Barr, D. B., and Needham, L. L. (2004). Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-IH). J Expo Anal Environ Epidemiol 14, 457-465. 

Step 3 calculate ER3 (the current excretion rate of creatinine corrected for non-steady-state conditions) ... 

Analysis of urine samples allows elimination rates of the chemical or its metabolite(s) to be ascertained. However, measurements in urine require specimen collection under a schedule (first morning urine, or 24-hour sample) that can create logistical difficulties. The concentration of the contaminant, or its metabolite(s), is usually corrected for the dilution of the urine (specific gravity or, more commonly, creatinine correction) to be used as a measure of dose. 

Trichloroacetic acid (TCA) in urine voided at the end of the workweek. This index is recommended only as a screening test because of the variability associated with urinary excretion of TCA and, as sueh, no creatinine correction is necessary. 

Yu CH, Yu CF, Tam S, Yu PH. Rapid screening of tetrodotoxin in urine and plasma of patients with puffer fish poisoning by HPLC with creatinine correction. Food Addit Contam 2010 27 89-96. 

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