Aminoglycoside and nephrotoxicity

Area of Science:

• Nephrology
• Pharmacology
• Toxicology

Background:

• Aminoglycosides are widely used antibiotics.
• Nephrotoxicity is a known side effect of aminoglycosides.
• The impact of aminoglycosides on renal acid excretion is not fully understood.

Purpose of the Study:

• To investigate the effects of gentamicin, netilmicin, and amikacin on renal acid excretion in male rats.
• To compare the nephrotoxic potential of these aminoglycosides.
• To assess the implications for clinical use during metabolic acidosis.

Main Methods:

• Male rats were administered doses of gentamicin, netilmicin, and amikacin equivalent to clinical doses.
• Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and U/P inulin ratio were measured under normal and acidotic conditions.
• Net acid excretion (BH) and urine-blood pCO2 were assessed.

Main Results:

• Gentamicin administration led to decreased GFR, ERPF, and U/P inulin ratio, indicating higher nephrotoxicity compared to amikacin and netilmicin.
• Net acid excretion (BH) decreased significantly after an acute acid load, irrespective of the aminoglycoside used.
• The distal tubule function, assessed by urine-blood pCO2 elevation after alkaline overload, remained largely unaffected.

Conclusions:

• Gentamicin exhibits greater nephrotoxicity than amikacin and netilmicin in rats.
• Aminoglycoside use during metabolic acidosis warrants caution due to potential acid retention.
• Further research is needed to understand the clinical implications of these findings.