Renal Parenchymal Accumulation of Aminoglycoside Antibiotics in Rats

Luft, Friedrich C.; Kleit, Stuart A.

doi:10.1093/infdis/130.6.656

Cited by 189 publications

(76 citation statements)

References 10 publications

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“…Other effects of gentamicin such as phospholipidosis, oxidative stress, extracellular calcium sensing receptor stimulation, and energetic catastrophe have been also connected with cell death. It has been showed that primary retention of gentamicin in proximal tubular cells following production of oxygen-associated metabolites and free radicals precedes gentamicin-induced nephrotoxicity (13,15,18,23). Besides, indirect effects of gentamicin, such as reduced renal blood flow and inflammation, may also contribute or amplify its cytotoxicity (19).…”

Section: Discussionmentioning

confidence: 99%

Experimental gentamicin-induced nephrotoxicity in the sheep

Fartashvand

Mousavi

Hajisadeghi

2014

Bulletin of the Veterinary Institute in Pulawy

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The aim of the study was to investigate the nephrotoxic effects of gentamicin in adult male sheep, and to identify the earliest signs of toxicity and the extent of clinical and biochemical changes. Twenty clinically healthy yearling male Iranian fattailed sheep were injected with gentamicin sulfate at a daily dose of 80 mg/kg for 9-10 d when nephrotoxicosis was induced. Blood samples were collected weekly before and after induction of nephrotoxicosis. Gentamicin-induced nephrotoxicity was characterised by increased creatinine and urea levels in serum, electrolyte imbalances, occurrence of albuminuria, and renal dysfunction. Significant elevation in respiratory and heart rates were observed one week after treatment (P < 0.05). There was a noticeable increase in water consumption, lethargy, and loss of appetite in treated sheep. There were significant correlations between serum creatinine and potassium (P = 0.004, r = 0.759), sodium (P = 0.017, r = 0.501), and urea (P = 0.021, r = 0.617) levels. Additionally, significant negative correlations between serum total protein and albumin and creatinine (P = 0.023, r = -0.484) and urea (P = 0.036, r = -0.381) were found. At necropsy, the kidneys were pale, swollen, and wet on the cut surface, especially perirenal tissues and ureters were oedematous. These findings confirmed the previous reports in other species.

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Section: Discussionmentioning

confidence: 99%

Experimental gentamicin-induced nephrotoxicity in the sheep

Fartashvand

Mousavi

Hajisadeghi

2014

Bulletin of the Veterinary Institute in Pulawy

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“…Serum creatinine may be used to estimate gentamicin clearance (14). All four aminoglycosides accumulate in the renal cortex although gentamicin shows a greater tendency for accumulation than the others (2,7,19). From animal studies, aminoglycosides which show greater tendency to accumulate tend to be more nephrotoxic (19).…”

Section: L I N I C a L Pharmacokineticsmentioning

confidence: 99%

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Mathews

Bailie

1987

J Clin Pharm Ther

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This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs.A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed.We review the lack of standardization of definitions for aminoglycosideassociated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed.The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.

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“…Aminoglycosides specifically accumulate in epithelial cells of the renal proximal tubule and in hair cells of the inner ear causing a variety of deleterious effects and eventual cell death (3)(4)(5)(6)(7)(8)(9). In recent years, changes in treatment regimens such as single daily dosing and monitoring procedures reduced the risk associated with aminoglycoside therapy.…”

mentioning

confidence: 99%

Megalin Deficiency Offers Protection from Renal Aminoglycoside Accumulation

Schmitz¹,

Hilpert²,

Jacobsen³

et al. 2002

Journal of Biological Chemistry

192

119

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Aminoglycosides are antibiotics commonly used to treat life-threatening Gram-negative bacterial infections. However, their use is hampered by their severe nephrotoxicity due to accumulation in renal proximal tubules. Several pathways have been implicated in the renal uptake of aminoglycosides including megalin, an endocytic receptor in proximal tubular cells. Here, we have used mouse models with genetic or functional megalin deficiency to explore the contribution of megalin and other pathways to renal aminoglycoside uptake in vivo. We demonstrate that the uptake of aminoglycosides into the kidney directly correlates with renal megalin activity and is completely eliminated in mice lacking the receptor. Thus, our studies provide unequivocal evidence that megalin is the only major pathway responsible for renal aminoglycoside accumulation and that the receptor represents a unique drug target to prevent aminoglycoside-induced nephrotoxicity in patients.

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Renal Parenchymal Accumulation of Aminoglycoside Antibiotics in Rats

Cited by 189 publications

References 10 publications

Experimental gentamicin-induced nephrotoxicity in the sheep

Experimental gentamicin-induced nephrotoxicity in the sheep

Clinical Pharmacokinetics, Toxicity and Cost Effectiveness Analysis of Aminoglycosides and Aminoglycoside Dosing Services

Megalin Deficiency Offers Protection from Renal Aminoglycoside Accumulation

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