Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney

1986 ◽  
Vol 70 (6) ◽  
pp. 595-599 ◽  
Author(s):  
P. J. Ratcliffe ◽  
M. P. Esnouf ◽  
J. G. G. Ledingham
Keyword(s):  
Rat Kidney ◽  
Tubular Reabsorption ◽  
Renal Tubules ◽  
Immunoglobulin Light Chain ◽  
Renal Handling ◽  
Water Excretion ◽  
Isolated Perfused Rat Kidney ◽  
Saturation Kinetics ◽  
Perfused Rat Kidney ◽  
Kinetics Of

1. The renal handling of myoglobin has been studied in the isolated perfused rat kidney. 2. Myoglobin was freely filtered. Reabsorption by the renal tubules showed saturation kinetics with a relatively low maximum rate of reabsorption (Tmax) of 27-30 μg min−1 g−1 wet wt. at a perfusate concentration of 70-80 μg/ml. Myoglobin reabsorption is therefore much less than that reported for immunoglobulin light chain or lysozyme in this model. 3. Large increases in sodium and water excretion produced by omission of oncotic agent from the perfusate did not alter the kinetics of myoglobin reabsorption. 4. The use of bovine serum albumin as oncotic agent in the perfusate prevented the tubular reabsorption of myoglobin. Small amounts of albumin are filtered by the isolated perfused kidney and it is postulated that this albumin interferes with tubular reabsorption of myoglobin.

scholarly journals Renal Disposition of Colistin in the Isolated Perfused Rat Kidney

2009 ◽  
Vol 53 (7) ◽  
pp. 2857-2864 ◽  
Author(s):  
Zheng Ma ◽  
Jiping Wang ◽  
Roger L. Nation ◽  
Jian Li ◽  
John D. Turnidge ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Tubular Reabsorption ◽  
Mean Values ◽  
Isolated Perfused Rat Kidney ◽  
Renal Disposition ◽  
Perfused Rat Kidney ◽  
Renal Clearances ◽  
The Mean ◽  
Potential Inhibitors

ABSTRACT Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 μg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CLR) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CLR/(f u × GFR), where f u is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 μM), Gly-Gly (833 μM), and HCl (2,500, 5,000, and 10,000 μM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.

Renal handling and effects of indomethacin in the isolated perfused rat kidney

1990 ◽  
Vol 183 (6) ◽  
pp. 2077
Author(s):  
P.G.F. Cox ◽  
M.M. Moons ◽  
F.G.M. Russel ◽  
C.A.M. van Ginneken
Keyword(s):  
Rat Kidney ◽  
Renal Handling ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Renal Handling of Tobramycin in the Isolated Perfused Rat Kidney

1994 ◽  
Vol 83 (5) ◽  
pp. 723-726 ◽  
Author(s):  
Tetsuya Aiba ◽  
Yoshie Itoga ◽  
Hiromasa Shimizu ◽  
Yusuke Tanigawara ◽  
Ryohei Hori
Keyword(s):  
Rat Kidney ◽  
Renal Handling ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

Indometacin: Renal Handling and Effects in the Isolated Perfused Rat Kidney

Pharmacology ◽  
1991 ◽  
Vol 42 (5) ◽  
pp. 287-296 ◽  
Author(s):  
Peter G.F. Cox ◽  
Miek M. Moons ◽  
Frans G.M. Russel ◽  
Cees A.M. van Ginneken
Keyword(s):  
Rat Kidney ◽  
Renal Handling ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

scholarly journals Renal Handling of Amphotericin B and Amphotericin B-Deoxycholate and Potential Renal Drug-Drug Interactions with Selected Antivirals

2014 ◽  
Vol 58 (10) ◽  
pp. 5650-5657 ◽  
Author(s):  
František Trejtnar ◽  
Jana Mandíková ◽  
Jana Kočíncová ◽  
Marie Volková
Keyword(s):  
Drug Interactions ◽  
Amphotericin B ◽  
Renal Excretion ◽  
Rat Kidney ◽  
Organic Anion ◽  
Transport Systems ◽  
Renal Tubules ◽  
Renal Handling ◽  
Cellular Models ◽  
Perfused Rat Kidney

ABSTRACTAmphotericin B (AmB) is excreted via the renal excretion route. This excretion process may result in nephrotoxicity. However, relevant information on the precise renal excretion mechanisms is not available. The aim of the study was to analyze the possible interaction of AmB or its prodrug AmB deoxycholate (AmB-DOC) with the typical renal organic anion transporters (OATs) and organic cation transporters (OCTs), using cellular and organ models. The relevant transport systems were then investigated in terms of the drug-drug interactions of AmB-DOC with antivirals that might potentially be used concomitantly. To analyze the renal excretion mechanisms of [3H]AmB, perfused rat kidney was employed. HeLa and MDCK II cells transiently transfected with human OAT1 (hOAT1) or hOCT2 were used as the cellular models. A significant tubular secretion of AmB was demonstrated in the perfused rat kidney. The cellular studies performed confirmed the active transport of AmB into cells. AmB did not interact with hOAT1 but strongly inhibited hOCT2. In contrast, AmB-DOC inhibited both hOAT1 and hOCT2. However, [3H]AmB cellular uptake by hOAT1 and hOCT2 was not found. AmB-DOC interacted significantly with adefovir, tenofovir, and cidofovir in hOAT1-transfected cells at supratherapeutic concentrations. In conclusion, the significant potency of AmB and AmB-DOC for inhibiting the transporters was demonstrated in this study. The secretion of AmB in the renal tubules is likely not related to the transporters here, since the drug was not proven to be a substrate for them. Drug-drug interactions of AmB and the antivirals used in this study on the investigated transporters are not probable.

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