Cadmium nephrotoxicity in human proximal tubule cell cultures

Human proximal tubule kidney cells grown in a serum-free tissue culture medium were exposed to concentrations of CdCl2 in a range of 0.5 to 10 micrograms/ml. Cells were observed from 1 to 20 d upon initiation of cadmium in the culture fluid. Both confluent and subconfluent populations of cells were treated and evaluated for cytotoxicity. Both populations exhibited a concentration-dependent toxicity to ionic cadmium. For cells treated with 2.0 to 10 micrograms/ml Cd, the decreases in cell numbers were largely irreversible. However, cells treated with Cd in a range of 0.5 to 1.0 micrograms/ml exhibited a partial recovery of cell number and control morphology. In this range, recovery was more efficient in the subconfluent cultures. Fine structural alterations in Cd-treated tubule cells included condensation of nuclear chromatin, loss of microvilli structure, disorganization of lateral membrane interdigitation, as well as decreased uptake of aminoglycoside antibiotics as evidenced by decreased numbers of myeloid bodies in these cells. The results of this study imply that use of a human proximal tubule culture system has potential in discerning structural and functional effects of cadmium as well as other nephrotoxic metals and compounds on the human kidney.