Effects of Dietary Electrolyte Supplementation on Gentamicin Nephrotoxicity

Aynedjian, Hagop S.; Nguyen, Dang; Sablay, Leonarda B.; Bank, Norman; Lee, Ho Yung

doi:10.1097/00000441-198805000-00006

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…This explains very well the aggravating effect of nonsteroidal anti-inflammatory drugs on aminoglycoside nephrotoxicity, since these drugs inhibit the production of the vasodilatatory prostaglandin PGE 2 (4). An increase in proximal intratubular free-flow pressure of single nephrons, most likely related to necrotic obstruction, has also been observed (5), suggesting that the decline of glomerular filtration has a multifactorial origin and involves a combination of tubular and nontubular mechanisms. The hypoosmotic polyuria, characteristic of the aminoglycoside toxicity, has been shown to result from the decreased fluid reabsorption by proximal tubules, secondary to an impaired solute reabsorption (64,105), evidenced by the ion-wasting phenomena described above.…”

Section: Renal Failurementioning

confidence: 89%

Aminoglycosides: Nephrotoxicity

Mingeot‐Leclercq

Tulkens

1999

Antimicrob Agents Chemother

686

428

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Aminoglycosides have long been one of the commonest causes of drug-induced nephrotoxicity (137). Although a clear recognition of the patient-and treatment-related risk factors (91), combined with the once-a-day schedule and effective monitoring procedures (98), have definitely improved the situation over what prevailed in the early 1980s (115), we are still short of having brought the safety of aminoglycosides to that of the main other wide-spectrum antibiotics. Chemical research aimed at obtaining intrinsically less toxic compounds has met with only modest success, and few of the other approaches proposed to reduce the toxicities of the available agents have reached practical clinical applications. Yet, because aminoglycosides are very effective antibiotics well suited to the treatment of severe infections (35), it seems important to maintain and even develop efforts to improve their therapeutic indices. The present minireview tries to present in a prospective way the status of both the basic and the clinical research on aminoglycoside nephrotoxicity in order to clarify the main issues and to pinpoint strategies that may eventually lead to their safer use. Ototoxicity, which is the second main adverse effect of aminoglycosides and which, in contrast to nephrotoxicity, is irreversible, will not be considered here since it has already been reviewed in this journal (52) and elsewhere (10). A companion minireview (83) examines and discusses the recent research dealing with the activities of aminoglycosides and bacterial resistance.on July 5, 2020 by guest http://aac.asm.org/ Downloaded from a Low doses refer to either clinical dosages for humans or of dosages less than 20 mg/kg per day for animals. b References are given as a source for illustration of the typical effect that is described or refer to review papers; see text for more comprehensive citations. c These alterations have often been used for the early detection of aminoglycoside insult; however, their measurement is of limited practical value in diseased patients. d These cells show markedly enlarged lysosomes, with a decreased buoyant density and prominent myeloid bodies. e Electron microscopy shows widespread alteration of the cell ultrastructure and subcellular organelles, including mitochondria, endoplasmic reticulum, and nuclei. f Myeloid bodies are abundant in lumen and urine. 1004MINIREVIEWS ANTIMICROB. AGENTS CHEMOTHER.on July 5, 2020 by guest http://aac.asm.org/ Downloaded from

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Section: Renal Failurementioning

confidence: 89%

Aminoglycosides: Nephrotoxicity

Mingeot‐Leclercq

Tulkens

1999

Antimicrob Agents Chemother

686

428

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“…The occurrence of renal failure is related to the duration of treatment and the total dose given. Constant awareness of the nephrotoxic potential of aminoglycosides is the key to the prevention of renal insufficiency: the physician should ensure that the patient is not volume depleted, and has normal serum electrolytes (Aynedjian et al 1988). Other risk factors include preexisting renal disease, hepatic disease with high bilirubin levels, age, volume depletion, depletion of potassium or magnesium, concomitant administration of other nephrotoxic drugs or concomitant renal ischaemia (Bennett & Porter 1990;Cooper & Bennett 1987;Desai & Tsang 1988;Humes 1988;Sawyers et al 1986;Smith et al 1986;Walker & Duggin 1988).…”

Section: Aminog/ycosidesmentioning

confidence: 99%

“…Recent studies have also provided evidence that the mode of administration is important: more fre-Drug Sa/ely 6 (2) 1991 quent dosing is less safe than dosing at longer intervals ). Recently, several studies have provided a whole array of possible new approaches to the prevention of aminoglycoside nephrotoxicity: coadministration of poly lysine or polyaspartic acid, which block gentamicin uptake ); supplementation with electrolytes (sodium, bicarbonate) and acetazolamide (Aynedjian et al 1988); combined administration with ticarcillin or carbenicillin ); and the use of calcium or calcium entry blockers (Humes et al 1984;Michael & Lee 1990). The outcome of aminoglycoside nephrotoxicity is usually good, most patients recovering renal function once the drug is stopped, although renal insufficiency may persist for some time because of drug accumulation.…”

Section: Aminog/ycosidesmentioning

confidence: 99%

Drug-Induced Nephrotoxicity Aetiology, Clinical Features and Management

1991

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There is a growing number of hospitalised patients who develop a drug-induced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. The 3 clinical syndromes that can be recognised in drug-induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. The first can be caused by prerenal problems, acute interstitial nephritis, acute tubular necrosis and intratubular obstruction. The most important drugs that cause prerenal failure are NSAIDs, captopril and cyclosporin. NSAIDs inhibit the synthesis of prostaglandins, and consequently vasoconstriction of the afferent arteriole leads to lowering of the glomerular filtration rate (GFR); captopril blocks the formation of angiotensin II (which also leads to a lower GFR), and should be used with caution in patients with stenotic renal arteries; cyclosporin causes vasoconstriction of the afferent arteriole, which is probably mediated by the sympathetic system. Combinations of these drugs result in increased nephrotoxicity. The drugs most likely to cause acute interstitial nephritis are antibiotics and NSAIDs. Normally, signs of an allergic reaction are also present. Acute interstitial nephritis is usually self-limiting, but in some studies it is claimed that steroids may promote recovery. Four important causal agents of acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents and cyclosporin. Approximately half of the cases of drug-induced renal failure are related to the use of aminoglycosides: generally, 10 days after start of treatment a nonoliguric renal failure develops, with recovery after withdrawal of the drug in almost all cases. The aminoglycosides are particularly nephrotoxic when combined with other nephrotoxic drugs. 80% of amphotericin B-treated patients develop renal insufficiency, a percentage that increases as the cumulative dose exceeds 5g. It is because of its unique antifungal properties that there are still some indications for the use of this highly nephrotoxic drug; the high percentage of nephrotoxicity can probably be prevented in part by sodium loading. The nephrotoxicity of radiocontrast agents is largely dependent on renal function: from 0.6% in patients with normal renal function to 100% in patients with a serum creatinine above 400 mumol/L. Diabetes mellitus does not add greatly to the risk of radiocontrast nephrotoxicity. The nephrotoxicity of cyclosporin is dose-dependent and reversible, although there are some reports of irreversibility after long term use. Cyclosporin can also result in nephrotoxicity in combination therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

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Efficacy and nephrotoxicity of aminoglycosides

Mattie¹

1991

Prevention in Nephrology

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Effects of Dietary Electrolyte Supplementation on Gentamicin Nephrotoxicity

Cited by 7 publications

References 20 publications

Aminoglycosides: Nephrotoxicity

Aminoglycosides: Nephrotoxicity

Drug-Induced Nephrotoxicity Aetiology, Clinical Features and Management

Efficacy and nephrotoxicity of aminoglycosides

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