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) wa s impaired in rats chronically treated with oral low-dose cadmium (Cd). Rat s (n = 15) were treated with 1 ppm of cadmium chloride added to drinking wa ter. We measured RFR (representing the ability to increase glomerular filtr ation rate [GFR] and renal plasma how [RPF] in response to infusion of glyc ine) at 2 and 10 months after initiation of exposure to Cd. Urinary excreti on of Cd was significantly higher in 10-month Cd-treated rats than in age-m atched control rats (provided with distilled water only). Weight gain was n oted in Cd-treated rats, which was identical to that in age-matched control rats. Urinary volume and urinary excretions of sodium, protein, and glucos e were similar in the two groups. There were no differences in the basal me an arterial pressure (MAP) and renal hemodynamics between 2-month Cd-treate d and age-matched control rats. Infusion of glycine resulted in significant increases in GFR and RPF and a significant reduction in renal vascular res istance (RVR) in both 2-month Cd-treated and age-matched control rats (cont rol, 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-mon th 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 no t change MAP, RPF, and RVR in both groups. In addition to age-related patho logical changes, mild renal interstitial edema and degenerative mitochondri a with diminished matrix density and loss of the cristae in the proximal tu bular cells were more frequent in 10-month Cd-treated rats. Our results sug gest that long-term oral intake of low-dose Cd in rats exacerbate age-relat ed impairment of renal functional reserve and degeneration of the proximal tubular epithelial cells. (C) 2000 Academic Press.