SYSTEMIC ALUMINUM TOXICITY - EFFECTS ON BONE, HEMATOPOIETIC-TISSUE, AND KIDNEY

Although the full mechanisms are not yet elucidated, research into the mechanism oi toxicity of aluminum (Al) on bone formation and remodeli ng and on hematopoietic tissue is ongoing. In contrast, little informa tion exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and prod ucing osteomalacia and adynamic bone disease. In contrast, while very low levels oi Al are mitogenic in bones oi experimental animals, the e ffect of low levels of Al in humans is unknown. Aluminum has been show n to have its mitogenic action at the osteoblast, but whether the effe ct on resorption is via osteoblast-directed changes in osteoclast acti vity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels pla y a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have be en reported to accumulate excess iron, without incorporating it into f erritin or heme. It is not yet known which steps in iron metabolism ar e disrupted by Al, ii they involve a single mechanism of action, or ev en ii this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephroto xicity; there are almost no studies in this area. Furthermore, researc h is needed to evaluate mechanisms of renal Al excretion, presently sh own by one study to occur at the distal tubule. Such studies might wel l throw light on whether Al plays a role in aggravating renal insuffic iency or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summar y, while a number of mechanisms have been proposed for the toxic actio n of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1.