Morphometric, biochemical, and physiological assessment of perinatally induced renal dysfunction

Three chemicals, known either to alter renal development when administered during fetal development or to affect renal function when administered to adult rats, were administered to Sprague-Dawley rats at critical periods of renal development. Chlorambucil (CHL) was administered ip on d 11 of gestation at doses of 0, 3, and 6 mg/kg; nitrofen (2,4-dichlorophenyl p-nitrophenyl ether) (NIT) was given po on d 8-16 of gestation at 0, 4.17, 12.5, and 25 mg/kg . d; and mercuric chloride (MER) was given sc on postnatal d 1 at 0, 14, and 28 micrograms/pup. To assess the effects of these toxicants on the functional development of the kidneys, a diuresis test with and without antidiuretic hormone was applied on postnatal d 3 (PD 3); a hydropenia test on PD 6; and kidney weights, glomerular counts in midhilar cross sections, and the specific activity of renal alkaline phosphatase were determined on PD 3 and 6. Data from pups with obvious malformations of the kidneys was eliminated from the statistical analyses of the data so that emphasis could be placed on alterations of functional development in individuals with apparently morphologically normal kidneys. CHL retarded the growth and biochemical differentiation of the kidney at 6 mg/kg. Pups from this treatment groups showed an attenuated response to exogenously administered antidiuretic hormone. NIT impaired growth and altered renal morphology at a dose of 12.5 mg/kg . d and altered physiological responses in the absence of anatomical changes at a dose of 4.17 mg/kg . d. MER, at doses near the maximum tolerated, failed to alter any parameter, indicating that the very young animal differs markedly from the adult in response to that compound. The data indicate that relatively simple tests of renal function are useful in the detection of perinatally induced nephrotoxicity.