Fractional Excretion Methods

Since one of the kidney s primary functions is maintaining electrolyte and mineral homeostasis in the face of fluctuating dietary intake and body needs, examination of plasma and urine electrolyte levels will provide some insight into renal function. Because of the large functional mass of the kidney, decrements in plasma electrolyte levels are usually not detected until the amount of renal functional diminution is significant. In contrast, urine electrolyte levels examined with knowledge of plasma levels and dietary intake can serve as an extremely sensitive index to the effect of drugs or chemicals on the functional state of the kidney. 

In animal studies the diet can be carefully controlled and thus the intake (and hence the plasma electrolyte levels) can be assumed to be fairly constant. Provided there are no sources of significant electrolyte loss resulting from the experimental manipulations (e.g., 

The most useful way to utilize urine electrolyte information is to calculate the fractional excretion (FE), which is the proportion of the filtered load that is excreted from the plasma. If both tubular function and plasma electrolyte values are normal, increases in electrolyte FE values clearly reflect a decrement in GFR. With tubular malfunction, the direction of the change in FE values depends on the net direction of electrolyte transport (i.e., FE will increase for electrolytes that are primarily reabsorbed and will decrease for secreted electrolytes) (Finco 1997 Stockham and Scott 2002). 

FE assessments can be performed in any species, as it requires only carefully timed complete urine collections and a concurrent assessment of GFR. FE will be unitless if the urine collection period is expressed in minutes, thus (Finco 1997)  

To eliminate the need for both complete timed urine collections (difficult to do in most animals) and concurrent assessment of GFR, FE values are usually calculated based on point-in-time urine collections by using creatinine excretion during the same time period as an estimator of GFR (Finco 1997). 

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Kaplan AA, Kohn OF. Fractional excretion of urea as a guide to renal dysfunction. Am J Nephrol 1992 12 49-54. Brochner-Mortensen J. Routine methods and their reliability for assessment of glomerular filtration rate in adults. Danish Med Bull 1978, 25 181-202. 

Lefebvre, H. P, O. Dossin, C. Trumel, and J. P. Braun. 2008. Fractional excretion tests A critical review of methods and applications in domestic animals. Veterinary Clinical Pathology 37 4-20. 

Measurement of fecal excretion of isotopic bile acids (65) gives only the half-life of the labeled bile acid used. The isotope is injected intravenously, and the daily fecal excretion of radioactivity is measured. According to this procedure, the fractional excretion rate of cholic acid in man is normally about 12-13% per day (66,67). Disadvantages of the method are that the absolute values are not obtained, the cholic and chenodeoxycholic acid excretions must be measured separately or a double label method must be used, and the fecal flow should be regular, though an unabsorbable fecal marker can be used. The method appears to be suitable for screening of ileal dysfunction. 

The answer is e. (Hardman, p 21J The fraction of a drug dose absorbed after oral administration is affected by a wide variety of factors that can strongly influence the peak blood levels and the time to peak blood concentration. The Vd and the total body clearance (Vd x first-order fte) also are important in determining the amount of drug that reaches the target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors it is the most reliable and popular method of evaluating bioavailability... 

Discussion We gave low dose BZ, since the purpose was primarily to measure the amount of BZ excreted intact in the urine, and to test the reliability and sensitivity of the urinary assay method, developed by Kondritzer Animal studies had indicated that only a small fraction of injected BZ was recoverable from urine. Human excretion results likewise showed the fraction of intact drug in the urine to be quite small with most of the BZ consisting of its metabolites. Clinical measures consisted only of general observation and periodic vital signs. Behavioral changes were mild. (The potency of the BZ used in these early studies was found to be less than 90% of the stated value. We were provided with a purer batch for subsequent studies.)... 

Polarographic methods have been extremely useful for the determination of the urinary excretion of the 1,4-benzodiazepines. An assay that employs selective solvent extraction and acid hydrolysis of diazepam and its major metabolites, iV-desmethyldiazepam and oxazepam, to their respective benzophe-nones has been employed to measure the urinary excretion of diazepam [183]. A pulse polarographic assay has been reported that will measure the urinary excretion of bromazepam following a single 12-mg dose [184]. The assay employs selective extraction of bromazepam and the 2-amino-5-bromobenzoyl-pyridine metabolite from the deconjugated metabolites, 3-hydroxybromazepam and 2-amino-3-hydroxy-5-bromobenzoylpyridine, into separate diethyl ether fractions. The residues of the respective extracts are dissolved in phosphate buffer (pH 5.4) and analyzed by pulse polarography, which yields two distinct... 

The most commonly used approach to quantify the concurrent flux of algal exudates to heterotrophic bacteria is to combine the 14C-tracer method with a differential filtration step in which free-living bacteria are physically separated from phytoplankton and excreted DOM (reviewed by Baines and Pace, 1991). The data presented in this review indicate that, on average, 46% of the excreted DOM is incorporated by bacteria. One limitation of this approach is that bacteria attached to particles are largely excluded from the analysis, but this can, to some extent, be overcome by monitoring the distribution of heterotrophic bacteria in both size fractions (Sondergaard et al., 1985). 

True absorption can also be determined by correcting net absorption for endogenous fecal excretion (26). Net absorption is measured by subtracting fecal isotope excretion from isotope intake. It is by far the most reliable method for fractional absorption measurements with Mg, given the limitations of Mg detection by EIMS. 

Jaundice does not necessarily accompany cholestasis. In severe and prolonged cholestasis, particularly if obstructive, jaundice is generally always in evidence. In cholestasis, the third fraction, known as delta bilirubin, can largely be detected by means of the diazo method. This fraction is firmly bound to albumin and can therefore only be dissociated and excreted slowly. For this reason, jaundice occurring together with cholestasis tends to subside at a significantly slower rate than the increased bile acid level in the serum. In this case, jaundice is due to a reflux of bilirubin from the canaliculus into the blood or a bidirectional transport of bilirubin via the sinusoidal membrane. Sometimes jaundice is caused by metabolic dysfunction of the liver cells. Bilirubin also acts as an antioxidant. 

Free or unbound cortisol represents the biologically active form of the circulating hormone, and its concentration is practically independent of alterations of its transport proteins. Various methods have been developed for estimating the free fraction in serum, but these assays are technically demanding, expensive, and not in general use. The measurement of urine free cortisol comes closest to providing an estimate of the free hormone concentration. As mentioned previously, approximately 2% of cortisol is excreted into the urine in a free form, and its measurement has been shown to be of use as a screening test for cortisol hypersecretion. However, P-hydroxycortisol has been reported to interfere with the immunoassay of free cortisol in urine. ... 

The fact that relatively large amounts of urea can be produced by subjects in whom an enzyme defect of the urea cycle has been proved has perplexed many investigators. Despite the fact that the activity of the rate-limiting enzyme has been reduced even to zero as measured by a sophisticated method, urea production still continues. It must therefore be concluded that, in all these cases, urea production is only impaired, not abolished. In all normal circumstances, all but a small fraction of the nitrogen in excess of tissue protein requirements is still excreted as urea and/or as the amino acid whose further metabolism is blocked. The impairment shows itself in the elevated levels of blood ammonia and consequently of glutamine, which vary according to the stress placed upon the urea cycle by varying the rates of protein intake. 

Methods for Determining Biomarkers of Exposure and Effect. Methods are available for the determination of 2-butoxyethanol in blood and urine (Johanson et al. 1986a Smallwood et al. 1984). The utility of 2-butoxyethanol as a biomarker of exposure is limited because of its short elimination half-time in blood (40 minutes) and the small fraction of the absorbed dose (less than 0.03%) excreted unchanged in urine (Johanson 1988 Johanson et al. 1986a). In contrast, the half-time of urinary 2-butoxyacetic acid was reported to be 5.77 hours after a controlled, 2-hour exposure to 2-butoxyethanol (Johanson et al. 1986a). The amormt of 2-butoxyacetic acid excreted in urine corresponded to 17-55% of the absorbed... 

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