The Isolated Perfused Rat Kidney Model: A Useful Tool for Drug Discovery and Development

Taft, David R.

doi:10.2174/1570163043484824

Cited by 35 publications

(39 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interference with glucose was completely attenuated by treatment with glucose oxidase, while the interference due to dextran was only partially attenuated through ethanol treatment. Of the perfusates investigated, only the 4% BSA/1.67% dextran combination preserved renal tubular function, adequate urine flow rate, and GFR in accordance with recommended threshold parameters [6]. Our data suggests that caution needs to be exercised when using either high glucose or dextran in combination with inulin as a marker for GFR.…”

Section: Resultssupporting

confidence: 56%

“…2). We confined these studies to a pumpdriven experimental setup in which all standard viability criteria were satisfied [6], and it was clearly superior to a gravity-driven system (Table 1). Here, the flow rate was adjusted in order to keep the arterial pressure within the range of 90 to 110 mmHg.…”

Section: Resultsmentioning

confidence: 99%

“…Traditionally, the isolated perfused kidney (iPK) has offered an informative system for investigating renal biology without the interference from other organs. The IPK was first established in 1876 by Bunge and schmeideberg and is commonly utilized as a screening tool for renal clearance and metabolism and to correlate renal drug deposition to renal function [6]. The functional integrity of the entire nephron is preserved, enabling the simultaneous determination of filtration, urinary excretion, and reabsorption, the three major parameters of renal function.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Isolated Perfused Rat Kidney: A Technical Update

et al. 2013

View full text Add to dashboard Cite

Abstract:The isolated perfused kidney is commonly utilized as a screening tool for renal clearance and metabolism, and to correlate renal drug deposition to renal function. Here, we report on several aspects of this procedure that will facilitate a higher experimental success rate and lead to a reduction in animal use. First, we investigated the utility of inulin and creatinine as commonly used markers to measure glomerular filtration rate. For inulin, in the presence of either 20 mM glucose or 4.5% dextran in the buffer, significant interference was observed using an anthrone-based colorimetric assay. These findings suggest that caution needs to be exercised when using glucose or dextran and when inulin is quantitated using this method. Under these circumstances the use of alternative methods of inulin quantitation such as fluorescently tagged inulin is preferred. Second, we optimized bovine serum albumin (BSA) and BSA/dextran compositions that are routinely recommended as oncotic agents in the perfusion buffer and found that a 4% BSA/1.67% dextran composition had the best viability of kidney biomarkers in accordance with recommended threshold parameters. These considerations will be of particular relevance to researchers utilizing the isolated perfused kidney as a screening tool to measure renal biology and drug metabolism as well as applications to investigate diabetic nephropathy.

show abstract

Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Isolated Perfused Rat Kidney: A Technical Update

et al. 2013

View full text Add to dashboard Cite

show abstract

“…17 Essentially, no MI absorption occurs beyond the short loop of Henle. 12 In contrast to inositol uptake studies in brush border membranes where SMIT2 is primarily expressed, 20 co-infusion of DCI into the late proximal segments of superficial nephrons only partially inhibits MI reabsorption in the loop of Henle. 17 These observations suggest that preferential reabsorption of MI compared to DCI occurs in the short loop thereby leading to the observed increase in DCI vs. MI excretion.…”

Section: Discussionmentioning

confidence: 94%

The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol

Chang

Choong

Phillips

et al. 2014

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 mM) and DCI (5 mM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease.

show abstract

“…The rabbit kidney was perfused at constant perfusion flow rate (15-20 ml/min) throughout the experiments. The perfusion fluid was a modified Krebs-Henseleit solution as described in a previous report [9] with the following composition: 141 mM Na Bovine serum albumin (BSA fraction V), 6 g/100 ml; 1 mM arginine, 1 mM alanine,1 mM glycine, 100 mg glucose, 50 mg inulin, and 100 mg LiCl were added to the solution resulting in a final perfusate volume of 100 ml. The pH of solution was adjusted to 7.4 and the perfusate in perfusion system was kept at 37 Ο C by a prewarming coil and oxygenation by the addition of a 1.2 μm filter in tissue bath for large organ chamber (Radnoti, chamber for organ isolation procedures, catalog No.…”

Section: Isolated Kidney Perfusion and Experimental Studiesmentioning

confidence: 99%

Acute effect of Russell’s viper (Daboia siamensis) venom on renal tubular handling of sodium in isolated rabbit kidney

et al. 2014

View full text Add to dashboard Cite

Background:The common complication in cases of poisoning by Russell's viper (Daboia siamensis) venom (RVV) is acute renal failure, but the pathogenesis involved in the alteration of kidney function is still not well understood. Objective: To clarify the role of RVV in the pathogenesis of renal damage, the present study examines the functional short-term alterations acutely induced by RVV in isolated perfused rabbit kidney. Methods: Effects of RVV on renal tubular handling of sodium including mean perfusion pressure (PP), the renal vascular resistance (RVR), the glomerular filtration rate (GFR), the urinary flow (V) and osmolar clearance (Cosm) were studied in two groups of isolated perfused rabbit kidneys; each group had four isolated rabbit kidneys. RVV was added to the perfusion system to obtain the final concentration of 10 g/ml. Results: Immediate decreases in PP and RVR caused by the venom were significantly apparent (p < 0.05) in the first 15 min after RVV administration. A gradual rise in both PP and RVR occurred 15 min after the initial reduction of the first phase, but its remained below pretreatment values. The GFR, V, and Cosm decreased significantly throughout experiments after venom perfusion (p < 0.05). The total fractional sodium excretion increased significantly after venom perfusion throughout experiments, while significant reductions (p < 0.05) of renal tubular handling of sodium were apparent for proximal absolute reabsorption of sodium and proximal fractional reabsorption of sodium including marked reductions of distal absolute reabsorption of sodium and distal fractional reabsorption of sodium of the venom treated kidney. Optical microscopy of treated kidney tissue showed acute tubular necrosis at the end of experiment. Conclusion: The present study suggests that an administration of RVV in the isolated rabbit kidney causes direct acute nephrotoxicity and acute alterations of main functional parameters that are probably mediated by either the direct action of venom components or an indirect effect from vasoactive mediators released from renal cells of the RVV-treated kidney.

show abstract

The Isolated Perfused Rat Kidney Model: A Useful Tool for Drug Discovery and Development

Cited by 35 publications

References 1 publication

The Isolated Perfused Rat Kidney: A Technical Update

The Isolated Perfused Rat Kidney: A Technical Update

The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol

Acute effect of Russell’s viper (Daboia siamensis) venom on renal tubular handling of sodium in isolated rabbit kidney

Contact Info

Product

Resources

About