Long-term oral intake of low-dose cadmium exacerbates age-related impairment of renal functional reserve in rats.

Our study was designed to clarify whether renal functional reserve (RFR) was impaired in rats chronically treated with oral low-dose cadmium (Cd). Rats (n = 15) were treated with 1 ppm of cadmium chloride added to drinking water. We measured RFR (representing the ability to increase glomerular filtration rate [GFR] and renal plasma flow [RPF] in response to infusion of glycine) at 2 and 10 months after initiation of exposure to Cd. Urinary excretion of Cd was significantly higher in 10-month Cd-treated rats than in age-matched control rats (provided with distilled water only). Weight gain was noted in Cd-treated rats, which was identical to that in age-matched control rats. Urinary volume and urinary excretions of sodium, protein, and glucose were similar in the two groups. There were no differences in the basal mean arterial pressure (MAP) and renal hemodynamics between 2-month Cd-treated and age-matched control rats. Infusion of glycine resulted in significant increases in GFR and RPF and a significant reduction in renal vascular resistance (RVR) in both 2-month Cd-treated and age-matched control rats (control, GFR: 133 +/- 10%, RPF: 148 +/- 8%; 2-month Cd-treated rats, GFR: 152 +/- 12% and RPF: 154 +/- 7%). The basal MAP and renal hemodynamics in 10-month Cd-treated rats were also identical to those in age-matched control rats. Infusion of glycine significantly increased GFR in 10-month control rats (132 +/- 15%), but not in 10-month Cd-treated rats (98 +/- 11%), but did not change MAP, RPF, and RVR in both groups. In addition to age-related pathological changes, mild renal interstitial edema and degenerative mitochondria with diminished matrix density and loss of the cristae in the proximal tubular cells were more frequent in 10-month Cd-treated rats. Our results suggest that long-term oral intake of low-dose Cd in rats exacerbate age-related impairment of renal functional reserve and degeneration of the proximal tubular epithelial cells.