What is the effect of aminoglycosides (antibiotics) on renal function, specifically regarding Impaired renal function (nephrotoxicity)?

From the Guidelines

Aminoglycosides should be avoided for the treatment of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available due to their potential to cause kidney damage (nephrotoxicity) 1. The use of aminoglycosides can lead to impaired renal function, and their administration should be carefully considered, especially in patients with pre-existing kidney disease or other risk factors for nephrotoxicity. Some key points to consider when using aminoglycosides include:

• Risk factors for aminoglycoside-induced nephrotoxicity, such as older age, dehydration, longer treatment duration, higher doses, and concurrent use of other nephrotoxic medications 1.
• The importance of therapeutic drug monitoring to minimize kidney damage, maintaining appropriate trough levels while ensuring effective antimicrobial coverage 1.
• The potential benefits of once-daily dosing regimens in reducing toxicity compared to multiple daily doses 1.
• The need for adequate hydration and avoidance of concurrent nephrotoxic agents to protect kidney function 1. It is essential to weigh the benefits of using aminoglycosides against the potential risks of nephrotoxicity and to consider alternative therapeutic options whenever possible 1. In patients with normal kidney function, aminoglycosides can be administered as a single dose daily rather than as multiple-dose daily treatment regimens to reduce the risk of nephrotoxicity 1. Monitoring aminoglycoside drug levels is also crucial when treatment with multiple daily dosing is used for more than 24 hours or with single-daily dosing for more than 48 hours 1.

From the FDA Drug Label

As with other aminoglycosides, gentamicin injection is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage of prolonged therapy Renal and eighth cranial nerve function should be closely monitored, especially in patients with known or suspected reduced renal function at onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug. Excessive peak and/or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity.

The effect of aminoglycosides, such as gentamicin, on renal function is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy.

• Key factors that increase the risk of nephrotoxicity include:
  • Impaired renal function
  • High dosage
  • Prolonged therapy
  • Advanced age
  • Dehydration
• Monitoring of renal function is essential, especially in patients with known or suspected reduced renal function, to prevent or minimize nephrotoxicity 2.
• Dosage adjustment or discontinuance of the drug may be necessary if signs of nephrotoxicity occur 2.

From the Research

Nephrotoxicity of Aminoglycosides

• Aminoglycosides can cause nephrotoxicity, which is a serious clinical problem 3, 4, 5, 6, 7
• The mechanism of renal toxicity is unclear, but aminoglycosides affect several nephron functions, including glomerular filtration, proximal tubular reabsorption, and urinary concentration 4
• The degree of toxicity appears to correlate with the level of renal tissue concentration of aminoglycoside 4

Risk Factors for Nephrotoxicity

• Volume depletion, advancing age, preexisting renal dysfunction, and exposure to other nephrotoxins increase the risk of nephrotoxicity 4, 6
• The cumulative dose, additional medication, and previous therapy with aminoglycosides also contribute to the risk of nephrotoxicity 3

Prevention of Nephrotoxicity

• Implementing a single daily dose regimen, adequate hydration, alkalization therapy with bicarbonate, monitoring of plasma trough levels, and minimization of the duration of therapy can prevent the development of renal impairment in most patients 3
• Administration of daily doses as one or two injections, rather than as multiple injections or by continuous infusion, may also decrease the risk of toxicity 6

Molecular Mechanisms of Nephrotoxicity

• Aminoglycosides are taken up in the epithelial cells of the renal proximal tubules and stay there for a long time, resulting in nephrotoxicity 7
• Acidic phospholipids and megalin, a giant endocytic receptor, play important roles in the binding and endocytosis of aminoglycosides in the proximal tubular cells 7

Incidence of Nephrotoxicity

• Aminoglycoside-induced acute renal failure occurs in 5-35% of patients treated with these drugs 3
• Aminoglycosides are the cause of the largest proportion of drug-induced acute nephrotoxicities, accounting for up to 10-30% of patients treated with these drugs 6