After a s.c. injection of 0.4 mg Cd/kg as
cadmium-metallothionein (
CdMT) in rats, a marked increase in urinary
protein concentration appeared at 16-40 h. There was a peak of urinary Cd content during the first 4 h after the treatment. Urinary Ca was increased at 8 h after the
CdMT injection and returned to normal level at 32 h.
Luminal and basolateral renal membrane vesicles were isolated from both control group and
CdMT (0.4 mg Cd/kg) group at 24 h after the injection.
Calcium uptake and binding of both fractions were decreased in the group treated with
CdMT. Cd, Zn and MT concentrations in the kidney cortex were increased, but Ca concentration was not significantly changed. Since injected
CdMT is probably only partly reabsorbed by tubular cells at the dose level of 0.4 mg Cd/kg as
CdMT, excessive plasma
CdMT is rapidly excreted in urine, explaining the increased Cd excretion during the first few hours observed in the present experiment. Decreased Ca binding in the
luminal membranes as observed in vitro could be one of the mechanisms of production of calcuria if occurring in vivo. Another possible explanation of calcuria is that Cd
ions released from
CdMT into the cytoplasm of the tubular cell, may exert ionic interference with Ca transport across the
luminal membranes and produce decreased Ca reabsorption. It is known that a disturbance of Ca metabolism could influence the membrane stability and such a change may contribute to explaining the
proteinuria characteristic of
CdMT nephrotoxicity. The reversibility of the
proteinuria observed after a single dose of
CdMT may be related to the induction of
metallothionein synthesis in the renal cells.