Increased urinary excretion of collagen metabolites in cadmium-metallothionein nephropathy.

In order to investigate the effect of cadmium-metallothionein (Cd-MT) on renal reabsorption of collagen metabolites, urinary excretion of hydroxylysine (Hyl), glucosyl-galactosyl-Hyl (Glc-Gal-Hyl), galactosyl-Hyl (Gal-Hyl), and hydroxyproline (Hyp), which are unique collagen metabolites, was determined in rats. Administration of Cd-MT resulted in acute renal failure in the form of proteinuria, aminoaciduria and glycosuria. Protein content in urine was greatly increased 1 day after injection of Cd-MT and decreased from 5 days, while the maximum levels of excretion of amino acids and glucose were observed at 6 days post-injection. The urinary excretion of total Hyp and Hyl, including Glc-Gal-Hyl, Gal-Hyl and free Hyl, were significantly increased at 3, 6 and 8 days after injection of Cd-MT with the maximum level at 6 days. Moreover, the molar ratio of Glc-Gal-Hyl/Gal-Hyl of urine in the Cd-MT-treated group was almost the same as that in the controls. These results suggest that a portion of Hyp, Hyl and its glycosides is normally reabsorbed from the renal tubule in the controls, and Cd-MT exposure caused an increase in urinary excretions of Hyp and Hyl, including its glycosides, through a renal tubular defect in reabsorption of Hyl in the same manner as with common amino acids.