Mechanism of acute renal failure after uranyl nitrate

Administration of 25 mg/kg uranyl nitrate (UN) to rats leads to a brief period of polyuria followed by progressive oliguria with death at 5 days. Factors that determine glomerular filtration rate (GFR) were examined in control Munich--Wistar rats (n = 16) and 2 h after either 15 mg/kg (n = 8) or 25 kg/kg (n = 7) of UN (i.v.) utilizing direct measurements of hydrostatic and oncotic pressures and plasma flow. Total kidney GFR was reduced to 47 percent of control in the low dose group and to 21 percent in the high dose group. The simultaneous nephron filtration rate (sngfr) was 28.6 +- 0.8 nl/min/g kidney wt in control, 29.1 +- 1.0 in the low dose group, and 18.1 +- 1.2 (P less than 0.001) in the higher dose group. Nephron plasma flow was equal to control at both doses of UN. Also directly measured hydrostatic pressure gradient across the glomerular capillary was not changed. The effective filtration pressure achieved equilibrium in control animals but became significantly positive at the efferent end of the capillary at both doses of UN and increased. Total glomerular permeability (L/sub p/A) was progressively reduced from control (0.089 +- 0.005 nl/s/g kidney wt/mm Hg) at low dose UN (0.047 +- 0.013) and high dose (0.024 +- 0.003 nl/s/g kidney wt/mm Hg). Therefore UN decreases GFR by two mechanisms: (a) tubular damage leading to back-diffusion of solutes and (b) a primary reduction in sngfr due to reduced L/sub p/A