The Influence of Age on Acute Renal Toxicity of Uranyl Nitrate in the Dog

Summary: The influence of age upon uranyl nitrate (UN) induced acute renal failure (ARF) was evaluated in 30 canine puppies 1–2 wk and 3–5 wk old. Renal function and morphologic studies were performed 2 h (initiation phase) and 24 h (maintenance phase) after UN administration. Age-matched controls received vehicle alone. Administration of UN to 1–2-wk-old puppies produced no changes in whole kidney glomerular filtration rate (GFR), despite a significant reduction in renal plasma flow (RPF) (P < 0.01). In contrast, during the maintenance phase, GFR was 60% lower than in the control group (P <; 0.02) whereas values for RPF were nearly identical to control values. In 3–5-wk-old puppies the magnitude of response to the heavy metal was much greater and GFR was nearly completely suppressed during the maintenance phase. This major alteration of GFR was independent of changes in RPF, because RPF remained similar to control values. Morphologic alterations consistent with the nephrotoxic effects of UN were observed in the proximal tubules of the most differentiated nephrons. These age-related morphologic alterations correlated well with the functional response (GFR) observed after UN administration, i.e., a proportionately greater degree of both morphologic and functional alterations followed the administration of the heavy metal in the oldest group of puppies.