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Effect of renal mass reduction on kidney tissue concentration of gentamycin following a single dose
M V Pahl1, N D Vaziri, P S Leitman
1University of California, Irvine MedicalCenter, Orange.
Abstract:
Controversy exists concerning the effect of pre-existing renal disease on aminoglycoside nephrotoxicity. Since nephrotoxicity appears to be related to gentamycin concentration in the renal tissue, we studied the effect of renal mass reduction on renal tissue gentamycin concentration. Four groups of male Sprague-Dawley rats, who had undergone progressive renal mass reduction, were studied after injection with a single dose of gentamycin. As expected, serum gentamycin concentration was increased in nephrectomized animals and showed significant inverse correlation with the weight of the residual renal tissue. However, urinary gentamycin secretion rate was proportional with the weight of the residual renal tissue. Renal tissue gentamycin concentrations in the nephrectomized animals were significantly higher than that found in the sham-operated controls. The data indicate that renal tissue gentamycin concentration attained after a single dose of the drug is higher in the presence of reduced renal mass.
Insights
Reduced kidney mass increases gentamycin concentration in renal tissue, potentially exacerbating aminoglycoside nephrotoxicity in patients with pre-existing renal disease.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Pre-existing renal disease complicates aminoglycoside therapy due to concerns about nephrotoxicity.
- Aminoglycoside nephrotoxicity is linked to drug concentration within renal tissue.
Purpose of the Study:
- To investigate the impact of reduced renal mass on gentamycin concentration in renal tissue.
- To determine if diminished renal function alters drug accumulation in the kidneys.
Main Methods:
- Male Sprague-Dawley rats underwent progressive renal mass reduction (nephrectomy).
- Animals received a single dose of gentamycin.
- Serum, urinary, and renal tissue gentamycin concentrations were measured.
Main Results:
- Serum gentamycin levels were elevated in nephrectomized rats.
- Renal tissue gentamycin concentrations were significantly higher in rats with reduced renal mass compared to controls.
- Urinary gentamycin excretion rate correlated positively with residual renal tissue weight.
Conclusions:
- Reduced renal mass leads to higher renal tissue gentamycin concentrations after a single dose.
- This finding suggests an increased risk of aminoglycoside nephrotoxicity in individuals with compromised kidney function.