Fetal nephrotoxicity

Investigation of fetal nephrotoxicity by maternally administered nephrotoxins is hampered by many constraints, including the maternal effects of the nephrotoxin, the ability of the nephrotoxin to cross the placenta and the difficulties associated with direct fetal intervention. In the pouch young of the North American opossum, Didelphis virginiana, we describe the toxic effects of a heavy metal on the immature metanephric kidneys. Varying doses of uranyl nitrate, a heavy metal salt, were administered to opossum pups in the pouch approximately 20 days after birth and the kidneys were harvested 3 to 12 days later for histological analysis. Group 1 consisted of 4 untreated and 5 saline treated pups. Group 2 (9 pups) received 10 to 15 mg./kg. intraperitoneal uranyl nitrate. Group 3 (6 pups) were given a uranyl nitrate dose of 25 mg./kg. Group 4, the high dose group, received either 58 mg./kg. (3 pups) or 87 mg./kg. (3 pups) of intraperitoneal uranyl nitrate. Group 1 kidneys demonstrated no pathological changes except for some mild renal tubular vacuolization seen in the saline treated animals. In group 2 tubular dilatation and necrosis were present 3 days after treatment; tubular regeneration could be seen by day 7. In group 3 glomerular cystic changes, interstitial fibrosis and tubular regeneration were present by day 7. Some restoration of normal architecture occurred by day 12 with fibrosis apparent. Group 4 animals demonstrated much more pronounced cystic changes of glomeruli and tubules as early as day 5 with marked interstitial fibrosis and prominent tubular regeneration. By day 12 group 4 pups continued to demonstrate significant and severe glomerular and tubular cystic changes with marked interstitial fibrosis. Inflammation, although present in all groups (except control), was never prominent. This first description of the effect of heavy metal toxicity on the immature metanephric kidney could provide an insight into the mechanisms of disordered kidney growth.