Related Experiment Videos
Inhibition of tobramycin reabsorption in nephron segments by metabolic alkalosis
1Department of Physiology, University of Ottawa, Ontario, Canada.
Abstract:
Chronic metabolic acidosis appears to potentiate aminoglycoside induced nephrotoxicity and renal cortical accumulation while some, but not all, studies show that bicarbonate loading reduces nephrotoxicity. The purpose of the present study was to determine if reabsorption of tobramycin in proximal and distal nephron segments in vivo is altered by systemic pH. To test this possibility on the single nephron level, 24 nl samples of [3H] tobramycin were micro-injected into proximal and distal nephron segments, and its recovery was compared to that of [14C] inulin in rats undergoing osmotic diuresis with NaHCO3 or Na2SO4 containing HCl. Results were obtained in 66 tubules in 20 rats. Although plasma and urine pH were altered as anticipated in bicarbonate-infused and acid-infused animals, urine and late proximal tubule flow rates were similar. When animals were acid infused, 24.8 +/- 1.90% of [3H] tobramycin injected into proximal nephrons was reabsorbed compared to 7.5 +/- 1.56% (P less than 0.001) when the animals were bicarbonate-infused. When [3H] tobramycin was injected into distal tubules, 5.9 +/- 0.75% was reabsorbed in acid-infused rats while virtually none of the injected tobramycin, 0.43 +/- 1.59%, was reabsorbed by the distal nephron of bicarbonate-loaded animals. Our results provide evidence that tobramycin reabsorption by both proximal and distal nephron segments is substantially reduced by bicarbonate-infusion.
Insights
Systemic pH significantly impacts tobramycin reabsorption in the kidneys. Bicarbonate infusion markedly reduces tobramycin uptake in both proximal and distal nephron segments, suggesting a role in mitigating nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Physiology
Background:
- Aminoglycosides, like tobramycin, can cause kidney damage (nephrotoxicity).
- Metabolic acidosis may worsen aminoglycoside nephrotoxicity, while bicarbonate may reduce it, but evidence is mixed.
- Understanding tobramycin's kidney handling is crucial for managing its toxicity.
Purpose of the Study:
- To investigate how systemic pH affects tobramycin reabsorption in specific kidney tubule segments.
- To determine if bicarbonate influences tobramycin handling in the proximal and distal nephron.
Main Methods:
- Rats underwent osmotic diuresis with either sodium bicarbonate or a sodium sulfate/hydrochloric acid solution to alter systemic pH.
- Radioactive [3H] tobramycin and [14C] inulin were micro-injected into proximal and distal nephron segments.
- Tobramycin recovery was compared to inulin recovery to quantify reabsorption in different pH conditions.
Main Results:
- Systemic pH was altered as intended by bicarbonate or acid infusion.
- Tobramycin reabsorption in proximal tubules was significantly higher in acid-infused rats (24.8%) compared to bicarbonate-infused rats (7.5%).
- Distal tubule tobramycin reabsorption was also reduced by bicarbonate infusion (0.43%) compared to acid infusion (5.9%).
Conclusions:
- Bicarbonate infusion substantially decreases tobramycin reabsorption in both proximal and distal nephron segments.
- These findings suggest that altered systemic pH influences tobramycin's handling within the kidney.
- Reduced reabsorption under bicarbonate loading may contribute to decreased tobramycin-induced nephrotoxicity.