Renal Clearance Of P-aminohippurate Research Articles

Renal Expression and Function of Oat1 and Oat3 in Rats with Vascular Calcification

Background/Aims: Calcium overload in vascular smooth muscle is a highly pathogenic event, which progresses with advancing age. Old patients are polymedicated, and several pharmacotherapeutic agents circulate in the plasma as organic anions. The organic anion transporters 1 and 3 (Oat1 and Oat3) are present in renal basolateral membranes, which transport organic anions of pharmacological and physiological interest. This study was designed to evaluate the renal expression and function of Oat1 and Oat3 in rats with vascular calcification. Methods: Vascular calcification was induced by administration of a single dose of vitamin D₃ (300,000 UI/ kg b.w., i.m.) to male Wistar rats 10 days before the experiments. Oat1 and Oat3 expression was assessed by immunoblotting, immunohistochemistry and reverse-transcriptase polymerase chain reaction. The renal clearance of p-aminohippurate (PAH, a prototypical organic anion, substrate of Oat1 and Oat3) was measured by conventional clearance techniques. Results: Oat1 and Oat3 protein levels showed an increase in plasma membranes of renal proximal tubules of treated animals, where both transporters are functional. This could explain the increase observed in the renal clearance of PAH in treated rats. Conclusions: These results suggest the relevance of considering the existence of vascular calcification, which is common in ageing, when organic anion drugs are prescribed.

Characterization of the mechanisms involved in the gender differences inp-aminohippurate renal elimination in rats

Gender differences in the renal handling on drugs and toxins have received too little attention. In the present study, a variety of preparations were used to examine the basis for the greater effectiveness of the male kidneys in the elimination of p-aminohippurate (PAH) in rats. Renal clearance of PAH was significantly lower in female rats as consequence of its smaller filtered and secreted load. The gender difference in the filtered load may be accounted for the lower value of glomerular filtration rate (GFR) displayed by female rats as compared with males. The lower value of the renal blood flow observed in females might explain, at least in part, the decrease in the GFR and in the secreted load of PAH. In females, maximal uptake for PAH transport into renal basolateral membrane vesicles decreased to 52+/-9% (P < 0.05) and Michaelis-Menten constant for PAH uptake into renal brush border membrane vesicles was increased to 163+/-8% (P < 0.05). These changes might also explain the lower secreted load of PAH. The sex difference in the renal clearance of PAH was also evidenced by the reduced systemic clearance observed in female rats.

Measurement of normal renal artery blood flow: cine phase-contrast MR imaging vs clearance of p-aminohippurate.

The purpose of this study was to compare cine phase-contrast MR imaging with renal clearance of p-aminohippurate for measuring normal renal blood flow. A reliable technique for evaluation of renal hemodynamics would be useful for studying renal vascular diseases and the effects of treatment. Measurements of renal blood flow based on renal clearance of p-aminohippurate are limited in that the kidneys are not studied separately, temporal resolution is poor, and normal renal function is required. Bilateral oblique sagittal cine phase-contrast MR images were obtained simultaneously in 10 healthy adult volunteers, with the imaging planes oriented perpendicular to the left and right renal arteries in order to measure through-plane flow. Velocity encoding was 150 cm/sec (seven of 10 volunteers) and 100 cm/sec (eight of 10 volunteers). Axial cine phase-contrast images of the abdominal aorta above and below the origins of the renal arteries were obtained in six volunteers. In these cases, renal blood flow was determined by measuring the difference between suprarenal and infrarenal aortic flow. For all volunteers, renal clearance of p-aminohippurate was determined immediately after MR measurements. Renal blood flow measurements determined by using cine phase-contrast MR imaging were in close agreement with those determined by using clearance of p-aminohippurate. At a velocity encoding of 150 cm/sec, the mean difference was 69 ml/min (95% confidence interval, -31 to 169 ml/min). At a velocity encoding of 100 cm/sec, the mean difference was 39 ml/min (95% confidence interval, -100 to 177 ml/min). Aortic flow measurements using cine phase-contrast MR imaging appeared to be less reliable for determining renal blood flow than measurements in the individual renal arteries, with a mean difference of -75 ml/min (95% confidence interval, -381 to 231 ml/min) compared with renal blood flow determined by using clearance of p-aminohippurate. We conclude that cine phase-contrast MR imaging is a promising technique for noninvasive measurement of renal blood flow. Measurements agreed closely with those obtained by using clearance of p-aminohippurate. In addition, the MR technique is faster, can be used to measure unilateral or bilateral renal blood flow, and does not depend on renal function.

Characterization of the renal handling of p-aminohippurate (PAH) in the beagle dog ( Canis familiaris)

1. The renal clearance of p-aminohippurate (PAH) is the most commonly used method for estimation of renal blood flow in laboratory animals and in humans. 2. This study characterizes the renal handling of PAH in 11 beagle dogs and describes for this species critical parameters for the valid use of the renal PAH clearance technique to estimate renal blood flow. 3. PAH was given as a priming dose plus infusion rates of 0.01–6 mg/kg per min. 4. Steady-state plasma concentrations were achieved within 60 min. 5. Urinary excretion of PAH accounted for ⩾-90% of the PAH infused. 6. Plasma PAH concentrations increased linearly with dose. 7. Renal secretion of PAH exceeded filtered PAH at plasma PAH concentrations less than approx. 6 mg%. 8. The Tm PAH for renal PAH secretion was approx. 0.4 mg/kg per min. 9. At PAH infusion rates above Tm PAH the clearance of PAH decreased and asymptotically approached the value of the GFR.

Renal acid-base physiology in marine teleost, the long-horned sculpin (Myoxocephalus octodecimspinosus).

We have sought to define urinary acid-base excretion in the marine teleost using the long-horned sculpin, Myoxocephalus octodecimspinosus. Urine flow (1.7 ml.h-1.kg-1) is relatively high, and glomerular filtration rate is very low (2.9 ml.h-1.kg-1). The urine-to-plasma ratio of inulin is 2. Renal clearance of p-aminohippurate is very high (108 ml.h-1.kg-1); phosphate and divalent cations are also secreted. In this framework we found urinary pH to average 6.6, but infusion of acid or alkali elicited a pH range of 6.1-7.8. Untreated fish may also have alkaline urine; so it is not surprising that precipitates of calcium or magnesium phosphate are sometimes found in bladder. These are of fine sandy quality and never cause blockage. Infusion of buffer (imidazole) increased the concentration of titratable acid 11-fold and output 2.5-fold. Carbonic anhydrase inhibitors had no effect on any urinary component, and histochemical studies revealed that cytoplasm and membranes did not yield the specific cobalt stain for the enzyme. An alkaline load (NaHCO3) is rapidly dissipated by gill excretion, mediated in part by carbonic anhydrase. An acid load (HCl) is rapidly dissipated by gill excretion, not dependent on carbonic anhydrase, and some renal excretion. Comparison and contrast of the low rates of HCO3- reabsorption in the marine teleost (and elasmobranch) with those of mammals suggest strongly that renal carbonic anhydrase evolved in connection with these high reabsorptive rates beginning in freshwater fish and continuing through amphibia and birds.