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Effect of gentamicin on glomerular ultrastructure
Abstract:
Previous micropuncture experiments have shown that gentamicin reduces the glomerular Kf even at low doses. Light and transmission electron microscopy have failed to provide evidence of structural alterations to explain the observed decreases in Kf. To elucidate and effects of gentamicin on glomerular ultrastructure, we used both scanning and transmission electron microscopy to study the glomeruli of rats given gentamicin at 4 and 40 mg/kg/day for 10 days, as well as 20 mg/kg/day for 4 weeks. Observations were also made during recovery from gentamicin-induced renal injury. Scanning and transmission electron microscopy revealed that gentamicin induced striking reductions in endothelial fenestral diameter, density, and area. These changes were not appreciated by light microscopy. By quantitative measurements, the reductions in endothelial fenestral area were found to be parallel to the previously observed reduction in Kf. During recovery, the morphological alterations improved pari passu with functional recovery. Contrary to observations in other models of acute renal failure, gentamicin-induced glomerular injury was unique in that the visceral epithelial surface was not affected. The mechanisms by which gentamicin induces alterations in glomerular ultrastructure remain to be defined.
Insights
Gentamicin significantly reduces kidney filtration (glomerular Kf) by decreasing endothelial fenestrae, the small pores in kidney capillaries. These structural changes in the glomerulus correlate with reduced kidney function.
Area of Science:
- Nephrology
- Renal Physiology
- Toxicology
Background:
- Gentamicin, an antibiotic, is known to reduce glomerular filtration coefficient (Kf).
- Previous studies using light and transmission electron microscopy did not reveal structural changes to explain this reduction.
- The precise ultrastructural effects of gentamicin on the glomerulus remain unclear.
Purpose of the Study:
- To investigate the ultrastructural effects of gentamicin on rat glomeruli.
- To correlate observed morphological changes with functional alterations in glomerular filtration.
Main Methods:
- Scanning and transmission electron microscopy were used to examine glomeruli from rats treated with gentamicin at various doses and durations.
- Quantitative measurements of endothelial fenestrae were performed.
- Observations were made during recovery from gentamicin-induced injury.
Main Results:
- Gentamicin caused significant reductions in the diameter, density, and area of endothelial fenestrae.
- These fenestral changes were not detectable by light microscopy.
- The reduction in fenestral area directly correlated with the decrease in glomerular Kf.
- Glomerular injury improved with functional recovery.
- Unlike other models, gentamicin did not affect the visceral epithelial surface.
Conclusions:
- Gentamicin induces specific ultrastructural changes in glomerular endothelial fenestrae, explaining the reduction in glomerular Kf.
- These fenestral alterations are reversible and improve with functional recovery.
- The unique pattern of gentamicin-induced glomerular injury warrants further investigation into its underlying mechanisms.