Gentamicin-induced loss of basolateral surface area of rat proximal convoluted tubules.
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).
Jones
D B
DB
Department of Pathology, State University of New York, Syracuse.
Elliott
W C
WC
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005839:Gentamicins; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008247:Lysosomes / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D005839:Gentamicins; D003404:Creatinine