Kidney disease is generally thought to affect all segments of a nephron equally. Bricker and co-workers first proposed this as the Intact Nephron hypothesis in 1971, and evidence to date has usually supported this hypothesis. However, most supporting studies have involved severe
renal failure, which may not be suitable to differentiate effects on functional sites or to test the hypothesis. The work included here examines the effects of limited
renal failure on two separate functions of the nephron: glomerular filtration, as measured by
inulin clearance and proximal tubular organic
anion secretory function, as measured by
p-aminohippuric acid (PAH) clearance.
Renal failure was induced in rats by
intravenous administration of
uranyl nitrate, a nephrotoxin. Doses used were 0.3, 1.0, and 3.0 mg/kg rat
body weight. Five days later, rats were given an
intravenous infusion of PAH and
inulin. Renal clearance of each compound was calculated. Results obtained in these experiments show that, at the lowest
uranyl nitrate dose, PAH clearance was significantly decreased but
inulin clearance was not. The ratio of CLPAH/CLIN was decreased from 2.55 in control rats to 1.21 in rats given the low dose of nephrotoxin. At higher
uranyl nitrate doses, both clearance rates were significantly decreased and the ratio of CLPAH/CLIN remained close to 1.0. These results indicate that the active transport functions of the nephron can be differentiated from passive transport functions. Caution should be exercised in extrapolating renal disease changes in active renal secretion to changes in passive renal elimination and the reverse.