PubMed · 6036374
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B H Ewald. 1967. Renal function tests in normal beagle dogs.. https://pubmed.ncbi.nlm.nih.gov/6036374/
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A method is described to assess the accuracy of quantitative collection of urine in small experimental animals using implanted Alzet osmotic pumps for continuous release of specific urinary markers. The nominal pumping rate (10.00 +/- 0.15 microliters/h; mean +/- SEM) of 10 osmotic pumps was verified (9.96 +/- 0.12 microliters/h) in a 10-day in vitro assay in isotonic saline at 39.0 degrees C. Ten adult female mink (1100 +/- 34 g) had a 2-ml osmotic pump implanted intraperitoneally for 7 days while maintained in metabolic cages on a conventional mink diet. In 5 mink the pumps contained [3H]-labelled p-aminohippuric acid (PAH) only. The remaining 5 animals received a pump containing [3H]-PAH and [14C]-labelled inulin. The experiment was well tolerated by all animals. In fed animals, the amount of urine collected per day was not influenced by the osmotic pumps, whereas 24 h of fasting (water allowed) caused a dramatic fall in urinary volume. In 4 consecutive 24-h collections of urine (n = 10 animals) the recovery of [3H]-PAH was 70.8 +/- 3.6% (range: 52.0-87.2%), and urinary plus faecal water (= total) recovery of [3H]-PAH averaged 77.0 +/- 3.7% (range: 60.3%-94.3%). For [14C]-inulin (n = 5 animals) the urinary and total recoveries were 68.4 +/- 2.2% and 77.2 +/- 2.4%, respectively. In urine the 14C to 3H counts-ratio was almost identical to that of the infusion solution, indicating that metabolic decomposition of the markers was negligible. The results indicate that the daily recovery of suitable urinary markers, released by implanted osmotic pumps, provides a reproducible and valid measure of the accuracy achieved in quantitative collection of urine in mink and probably also in other animal species. Hence, this technique may be useful in future studies on animal nutrition and/or drug disposition.
Published data on the renal clearance of creatinine, p-aminohippuric acid (PAH) and kanamycin in relation to glomerular filtration rate (GFR) in patients with various renal diseases were analysed by a physiological model of renal clearance. Fitting of the data by the general linear equation representing the model proposed by Levy [10] resulted in insignificant intercepts with the ordinate, indicating the unsuitability of the model for the detection of tubular secretory activity. Use of this model also did not lead to significant improvement in goodness of fit compared to simple proportionality of renal clearance and GFR. On the other hand, parameter estimates of the physiological model obtained from the data by nonlinear regression analysis revealed statistically significant tubular secretion both of PAH and creatinine. The much lower tubular secretory activity estimated from the kanamycin data did not reach statistical significance. For compounds exhibiting statistically significant tubular secretion, use of the physiologically based relationship between renal clearance and GFR significantly improved the goodness of fit to the data as compared to simple proportionality of both variables. It is concluded that analysis of the relationship between renal clearance of drugs and GFR using the physiological model of renal clearance can contribute to our knowledge of drug handling by the kidney, and may facilitate drug classification according to total extraction by this organ.
Quinidine in vitro significantly reduced accumulation of TEA (tetraethyl ammonium) and PAH (p-amino hippurate) and inhibited oxygen consumption in renal cortical slices. Mitochondrial respiratory control index (RCI) and ADP/O ratio were decreased. Intraperitoneal administration of quinidine at 75 mg/kg twice a day for four days inhibited TEA transport in renal cortical slices and decreased oxygen consumption. Mitochondria showed a reduction in ADP/O ratio but no change in RCI. Serum biochemical measurements indicated a significant elevation in serum creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).