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Gentamicin-induced loss of basolateral surface area of rat proximal convoluted tubules
1Department of Pathology, State University of New York, Syracuse.
Abstract:
This study was performed to find the quantitative relationship between basolateral surface alterations of proximal convoluted tubules (PCT) and renal failure in 26 Fisher 344 rats receiving 20 mg/kg of gentamicin twice daily up to 28 days. They were sacrificed on day 14 (renal failure, 13 rats) and day 28 (recovering, 13 rats). Control rats were used for morphologic studies (19) and serum creatinine studies (6 of 19). PCTs (14th and 28th day) were graded as to severity with transmission electron microscopy into grades 1 (normal-mild injury), 2 (moderate injury) and 3 (severe injury) using brush border and basolateral surface alterations. Scanning electron microscopy confirmed these grades using kidney slices and isolated tubular cells. With scanning electron microscopy greater than 3400, PCTs were graded and counted from 14th and 28th day kidneys, day 14 (grade 1, 18%, grade 2, 22%, and grade 3, 60%), day 28 (grade 1, 89% grade 2, 4%, and grade 3, 7%). The basolateral surface contour lengths (BSCL) per length of underlying tubular basement membrane were measured using a computer-assisted digitizer on transmission electron microscopy prints. Control PCTs had a mean BSCL of 268 microns, SD +/- 79, SE +/- 19 per 40 microns of tubular basement membrane. Likewise, the mean BSCL of grade 1 tubules measured 249 microns, SD +/- 87, SE +/- 21; the mean BSCL of grade 2 tubules was 125 microns, SD +/- 40, SE +/- 9 and grade 3 tubules BSCL was 90.5 the BSAI values showed that the 14th day rats had 28% of control BSAI and 28th day rats 80%. 2, grade 3, p less than 0.005). Squaring the mean BSCL of each group gave a basolateral surface area index (BSAI). Combining the percentage of the 3 grades of tubules of 14th and 28th day rats with the BSAI values showed that the 14th day rats had 28% of control BSAI and 28th day rats 80%. Mean serum creatinines (milligrams/deciliters) were: 14th day, 0.86; 28th day, 0.54; and control, 0.39. These data indicate loss of function correlates with lower BSAI (decreased basolateral surface area).
Insights
Gentamicin-induced kidney injury in rats shows severe proximal convoluted tubule (PCT) damage and reduced basolateral surface area index (BSAI) during renal failure. Recovery leads to significant PCT repair and improved BSAI, correlating with kidney function restoration.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Gentamicin is an antibiotic known to cause nephrotoxicity.
- Proximal convoluted tubules (PCTs) are crucial for kidney function and susceptible to drug-induced damage.
- Understanding the structural changes in PCTs can elucidate mechanisms of renal failure.
Purpose of the Study:
- To quantify the relationship between basolateral surface alterations in PCTs and renal failure.
- To assess the reversibility of these structural changes upon recovery.
- To correlate structural changes with functional markers like serum creatinine.
Main Methods:
- 26 Fisher 344 rats received gentamicin (20 mg/kg twice daily) for up to 28 days.
- Transmission and scanning electron microscopy were used to grade PCT injury (grades 1-3).
- Basolateral surface contour lengths (BSCL) were measured, and a basolateral surface area index (BSAI) was calculated.
Main Results:
- On day 14 (renal failure), 60% of PCTs were severely injured (grade 3) with a mean BSAI of 28% of control.
- On day 28 (recovery), 89% of PCTs showed normal to mild injury (grade 1) with a mean BSAI of 80% of control.
- Serum creatinine levels were elevated during renal failure (0.86 mg/dL) and decreased upon recovery (0.54 mg/dL) compared to controls (0.39 mg/dL).
Conclusions:
- Significant PCT basolateral surface damage correlates with gentamicin-induced renal failure.
- The observed structural recovery of PCTs is associated with improved kidney function.
- BSAI serves as a quantitative marker for assessing nephrotoxicity and recovery.