The long-term effects of uranyl nitrate on the structure and function of the rat kidney

Studies were undertaken to determine the long-term effects of the nephrotoxin, uranyl nitrate, on the function and structure of the rat kidney. Animals were injected with 10 mg/kg B.Wt. of uranyl nitrate and renal function studies were performed one, two, four and eight weeks after drug administration. Light microscopy and scanning and transmission electron microscopy were used to characterize the morphologic changes at each time interval. Glomerular filtration rate was significantly reduced (P less than 0.01) one week (0.18 +/- 0.06 ml/min/100 gm B.Wt.) and two weeks (0.54 +/- 0.09 ml/min/100 gm B.Wt.) after drug treatment compared to controls (1.01 +/- 0.4 ml/min/100 gm B.Wt.) and returned to normal values by four weeks. The fractional excretion of sodium was significantly increased (P less than 0.01) one week after uranyl nitrate treatment (2.45% +/- 0.82) compared to controls (0.29% +/- 0.11). No further differences in this parameter were noted after one week. At all time intervals studied the pars recta of the proximal tubule (S2 and S3 segments) was the most consistently damaged region of the nephron. Acute tubular necrosis and tubular regeneration of these segments were evident one and two weeks after drug administration. Many of the tubules were widely dilated and lined by low-lying squamous epithelial cells. By four weeks some of these pars recta segments could be classified as microcysts and this type of lesion persisted as long as eight weeks after treatment. Regeneration of most injured proximal tubules was complete by eight weeks. Atrophic proximal tubules, marked interstitial fibrosis and a mononuclear cell infiltration, consistent with a chronic type of injury, were noted at the later time intervals. These results suggest that uranyl nitrate induces a persistent injury to the kidneys of rats causing lesions as long as eight weeks after injection.