This proposal continues and extends the original aims of HD 5572, to study kidney and volume homeostasis in pregnancy. Objectives of this 4 year proposal are: A) Measure kidney function, alterations in intravascular and extracellular volume, and the renal response to saline infusions in 1) rats with autologous immune-complex disease affecting primarily the renal glomerulus; 2) animals with chronic parenchymal kidney disease involving mainly the tubules; and 3) rats that have received renal allografts. In each of these models blood pressure will be monitored prior to and during gestation. Clearances of insulin and its volume of distribution, PAH and its extraction, the fate of injected labeled microspheres, and plasma volume will be measured in term-pregnant animals and age-matched controls. In separate experiments the ability to excrete a sodium load (estimated at 20% of anticipated extracellular volume) will be evaluated, and in most studies renal morphology including light, immunofluorescent, and electron microscopy will be evaluated and described. b) As an extension of the laboratory's goals, methods for the radioimmunoassay of vasopressin in plasma and urine will be perfected and this assay will be applied to experiments which aim at describing osmoregulation in pregnancy. 1) The effects of volume depletion and/or manipulation of osmolality will be studied in 14-day and term-pregnant rats, and in their virgin littermates. 2) Finally, the influence of water deprivation and loading, as well as that of a slow infusion of hypertonic saline on plasma ADH levels of pregnant women will be evaluated. Long-term goals are to apply information obtained from these studies towards improving the management of normal human pregnancy and of gestations complicated by hypertension and renal disease.