Renal type II Na/P-i-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium treated rats

The cellular mechanisms of cadmium (Cd) nephrotoxicity are poorly understood. In this study we investigated the cellular causes of the Cd-induced phosphaturia in the rat. Compared to controls, Cd-treated rats (2 mg Cd/kg body weight, s.c. for 14 days) showed a marked polyuria, proteinuria and phosphaturia. As studied by the rapid filtration technique in isolated cortical brush-border membrane vesicles (BBMV), Na+-gradient-driven uptake of phosphate ([P-32(i)]) and of [H-3] glucose were markedly decreased in Cd-treated rats, whereas uptake of sulphate ([S-35]) remained unchanged. By Western blotting of BBMV proteins and by indirect immunocytochemistry in 4-mu m thick frozen fixed kidney sections, using an antibody against the type II Na/P-i-cotransporter (NaPi-2), we found a diminished expression of this protein in the brush-border membrane from Cd-treated rats. However, the expression of the water channel aquaporin 1, estimated from the specific antibody staining in brush-border membranes, remained unchanged by Cd. Northern blot analysis showed a strong reduction of 2.7 kb NaPi-2-related mRNA in Cd-affected kidneys. Our data indicate that: (i) Cd may reduce reabsorption of P-i in proximal tubules by affecting the expression of the functional Na/P-i-cotransporters in the Luminal membrane, and (2) Cd effects on brush-border transporters are selective.