Renal handling of humanβ ₂-microglobulin in normal and cadmium-poisoned rats

Abstract

The renal handling of humanβ ₂-microglobulin (β ₂-m) was investigated in normal rat and in rat with cadmium-induced renal damage. Cadmium was administered either in drinking water at a concentration of 100 ppm for up to 16 months or by i. p. injection of 1 mg Cd/kg, five times a week for up to 4 months. When renal dysfunction has developed, namely after 2 and 10 months of the i. p. and oral treatment respectively, unlabelled humanβ ₂-m was injected intravenously and its disappearance in serum and its urinary excretion were studied by means of a sensitive immunoassay. In serum, the level ofβ ₂-m drops by about 90% during the 10 first min, then declines more slowly with a half life around 20 min. Serum disappearance curves ofβ ₂-m in normal and cadmium-treated rats did not differ markedly.

The amount ofβ ₂-m recovered in urine during the 4 h following the injection averaged 0.03% of the injected dose in normal rats. It increased on the average to 10% in rats treated i. p. with 1 mg Cd/kg for 3 months. However, in rats given 100 ppm Cd per os for 10 months, this amount averaged only 0.14%. A similar value was observed 5 months later, although at that stage, the critical level of cadmium in kidney cortex had been reached for 6–7 months. These data which were in accordance with the disturbances of the other renal parameters measured in cadmium-treated rats indicate that:

• 1) humanβ ₂-m is reabsorbed by rat kidney at a similar rate as by human kidney;

• 2) if the occurrence of cadmium tubulopathy is concomitant with the saturation of cadmium-binding sites in kidney, its severity depends greatly on the rate at which cadmium reaches the saturated kidneys.