Radioimmunoassay Measurement of Urinary Ligandin Excretion in Nephrotoxin-Treated Rats

Abstract

1. A radioimmunoassay was used to establish normal urine excretion of ligandin, a renal tubular protein, in rats, and to study the pattern of ligandin excretion after nephrotoxin administration. 2. Validation of radioimmunoassay measurement of ligandin in urine is described. A normal range of 2–46 ng/h was obtained for ligandin excretion in rats (n = 24). 3. Mercuric chloride (HgCl₂; 10 mg/kg) administration resulted in a significant increase in ligandin excretion within 6 h, preceding the onset of significant azotaemia. Serum ligandin concentrations were raised after 12 h, while renal ligandin concentration fell to 30% of control values by 24 h. 4. Rats given HgCl₂ (5 mg/kg) developed massive ligandinuria between 6 and 12 h, which declined to normal values by 72 h. Potassium dichromate (K₂Cr₂O₇; 7 mg/kg) administration produced a comparatively moderate increase in ligandin excretion after 24 h. 5. The time course of ligandin excretion in HgCl₂- and K₂Cr₂O₇-treated rats correlated with the histological sequence of damage to the pars recta and pars convoluta of the proximal tubule respectively. 6. The results of this study confirm that renal ligandin is confined mainly to the pars recta of the proximal tubule, and small quantities of this protein are present in the pars convoluta. Radioimmunoassay provides a sensitive and specific means for measuring ligandin in urine and provides a valuable tool for the detection and study of renal tubular damage.