The compartmentalization and metabolism of aluminum in uremic rats

Aluminum levels in bone are significantly higher and those in the liver are significantly lower in uremic rats than in control rats receiving similar amounts of parenterally administered aluminum. We evaluated the possibility that the hyperparathyroidism present in uremia might affect aluminum metabolism and toxicity. Uremia was induced by establishing the remnant kidney and hypoparathyroidism was induced by selective parathyroidectomy. Aluminum loading was accomplished by intraperitoneal aluminum injection. Bone aluminum concentration in the uremic group was 113 +/- 16 mg/kg, compared with 80 +/- 7 mg/kg in the uremic parathyroidectomy group and 55 +/- 9 mg/kg in controls (p less than 0.001 between all groups) and 52 +/- 16 mg/kg in parathyroidectomy controls. When parathyroidectomy was performed after the uremic animals were already loaded with aluminum, bone aluminum levels did not change, suggesting that the parathyroidectomy prevented some of the excess bone aluminum levels in uremia by decreasing bone uptake of aluminum rather than enhancing mobilization of bone aluminum. The only other effect the parathyroidectomy procedure had on tissue aluminum was to slightly decrease brain aluminum levels in uremic animals and kidney aluminum levels in control rats. Uremic rats with parathyroidectomy were found to have a significantly greater trabecular bone osteoid area than uremic rats (45.9% +/- 9.7% and 13.4% +/- 10.6%). We conclude that parathyroidectomy, especially in the uremic state, has a major influence on the compartmentalization of aluminum in bone and intensifies aluminum-induced osteomalacia.