Renal Insufficiency Associated with Gentamicin Therapy

Wilfert, James N.; Burke, John P.; Bloomer, H. Allen; Smith, Charles B.

doi:10.1093/infdis/124.supplement_1.s148

Cited by 90 publications

(37 citation statements)

References 4 publications

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“…Another patient developed a pruritic rash when tobramnycin was discontinued but the relationship of this eruption to tobramycin therapy was doubtful. Ototoxicity with gentamicin has been related to dose level, duration of therapy, renal function, and patient age (12,27). Although the factors relating to ototoxicity with tobramycin have not as yet been fully determined, in our patients the dose never exceeded 4.5 mg per kg per 24 h and the duration of therapy was not greater than 19 days.…”

mentioning

confidence: 59%

Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria

Jaffé

Ravreby

Meyers

et al. 1974

Antimicrob Agents Chemother

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mentioning

confidence: 59%

Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria

Jaffé

Ravreby

Meyers

et al. 1974

Antimicrob Agents Chemother

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“…However, because of their rarity it is difficult to determine whether this is causative or incidental (31)(32)(33)(34). Gentamicin causes acute tubular necrosis that may also be associated with tubulointerstitial changes seen on LM (35)(36)(37). EM changes with gentamicin also only constitute tubular injury (38,39).…”

Section: Discussionmentioning

confidence: 99%

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

et al. 2007

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Indomethacin, ibuprofen, and gentamicin are commonly administered to neonates between 24 and 28 wk gestation when glomerulogenesis is still occurring. Indomethacin is known to cause renal failure in up to 25% of infants treated. Possible morphologic effects of these drugs are largely unknown. The purpose of this study was to determine the type of renal changes found on light (LM) and electron microscopy (EM) following administration of indomethacin, ibuprofen, and gentamicin in a neonatal rat model. Rat pups were exposed to indomethacin or ibuprofen and/or gentamicin antenatally for 5 d before birth or postnatally for 5 d from d 1 of life. Pups were killed at 14 d of age. LM examination in all indomethacin-and ibuprofen-treated pups both antenatally and postnatally showed vacuolization of the epithelial proximal tubules, interstitial edema, intratubular protein deposition but no significant glomerular changes. EM examination showed pleomorphic mitochondria and loss of microvilli in the tubules. The glomeruli showed extensive foot process effacement and irregularities of the glomerular basement membrane. EM changes were most marked in pups treated antenatally with ibuprofen, and indomethacin with gentamicin postnatally. Indomethacin, ibuprofen, and gentamicin cause significant change in glomerular and tubular structure in the neonatal rat model. U p to 5% of infants are delivered between 24 and 28 wk gestation, at a time when glomerulogenesis is occurring. Indomethacin and ibuprofen are commonly used in extremely premature neonates to close a patent ductus arteriosus at this time (1,2). Both of these drugs are successful in closing the ductus (3,4), but the morphologic effects these drugs may have on the developing kidney are unknown. Both drugs are known to be nephrotoxic, with indomethacin causing acute renal failure in 25% of premature neonates treated (5). Ibuprofen is considered to have less renal toxicity than indomethacin, but is as efficacious as indomethacin at closing the patent ductus (6). Two animal studies have shown an effect on glomerulogenesis by ibuprofen and a COX-2 selective inhibitor. In both studies, the number and size of glomeruli was decreased (7,8).Gentamicin is frequently administered at the same time as indomethacin or ibuprofen. Gentamicin has been shown in in vitro studies to affect nephron development (9). The combination of nonsteroidal anti-inflammatory drugs (NSAID) and gentamicin on glomerular development is unknown. The renal effect of indomethacin has not been examined in a neonatal animal model, nor has the combination of both indomethacin or ibuprofen and gentamicin.In the human, glomerulogenesis is complete at 36 wk gestation. The metanephron develops at 5 wk gestation, with vesicular glomeruli development occurring at 18 wk gestation. Glomerular tubular development occurs from 24 wk gestation and is complete at 36 wk (10 -12). In the rat model, glomerulogenesis continues after birth until 14 d of life (13). At birth the neonatal rat kidney is similar to that of a ...

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“…Gentamicin-induced nephrotoxicity has been documented in man (10,25,37), as expressed by elevations in blood urea nitrogen and serum creatinine levels. In rats (11,19) and dogs (3), histopathological studies have shown that gentamicin caused tubular necrosis in the proximal convoluted tubule.…”

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confidence: 99%

Renal Extraction of Gentamicin in Anesthetized Dogs

Chiu¹,

Brown²,

Miller³

et al. 1976

Antimicrob Agents Chemother

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The tubular handling of gentamicin (G) and its intrarenal distribution were determined to elucidate the mechanism of G accumulation in the kidney. At a serum level of 11.1 ± 0.5 μg/ml (10 animals), as maintained by constant infusion for 5 h, serum Na + and K + , arterial pressure, effective renal plasma flow and glomerular filtration rate remained undisturbed. The clearance values in milliliters per minute for G, inulin, and p -aminohippuric acid were 40.3 ± 1.8, 49.9 ± 2.8, and 132 ± 14, respectively. The ratio of clearance of G to clearance of inulin was 0.82 ± 0.04 ( P < 0.005), suggesting net reabsorption of G by the renal tubules. The renal cortex/serum ratio for G was 11.9 ± 2.1, and the medulla/serum ratio was 2.7 ± 0.4, indicating greater uptake of G by the cortex. The extraction ratio of p -aminohippuric acid was 0.74 ± 0.03. In contrast, the extraction ratio of G was 0.20 ± 0.03, which was significantly lower than that of inulin (0.30 ± 0.04). It is concluded that the accumulation of G in the cortex was due to tubular reabsorption. Probably some of the reabsorbed G became trapped in the epithelial cells after crossing the luminal membrane, whereas some returned to the circulation.

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Renal Insufficiency Associated with Gentamicin Therapy

Cited by 90 publications

References 4 publications

Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria

Clinical Study of the Use of the New Aminoglycoside Tobramycin for Therapy of Infections Due to Gram-Negative Bacteria

Renal Glomeruli and Tubular Injury Following Indomethacin, Ibuprofen, and Gentamicin Exposure in a Neonatal Rat Model

Renal Extraction of Gentamicin in Anesthetized Dogs

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