Hyperphosphatemia: pharmacologic intervention yesterday, today and tomorrow.

Control of serum phosphorus continues to be of utmost importance in renal replacement therapy, due to the high prevalence of hyperphosphatemia in the dialysis population. Hyperphosphatemia has traditionally been associated with secondary hyperparathyroidism, soft tissue calcification, and renal osteodystrophy. Recent evidence implicates poor phosphorus control as an important factor in the development of cardiovascular calcification, cardiac disease, and death in patients with chronic renal failure. Dietary restriction of phosphorus, while an important factor in the control of serum phosphorus, has practical problems that limit its success in most patients. Aluminum was used in the past to inhibit phosphorus absorption, but its accumulation has serious, toxic effects on bone. Calcium-based binders have largely replaced aluminum; however, these binders are limited by the excessive amounts of calcium absorbed, which can frequently lead to positive calcium balance, suppression of bone turnover, and hypercalcemia. Calcium overloading is also associated with soft tissue and cardiovascular calcification. More recent strategies for managing hyperphosphatemia and renal bone disease include the use of nonabsorbed phosphate binders that are aluminum- and calcium-free and the development of vitamin D analogs that control parathyroid hormone activity with less calcemic effects. Future goals include defining optimal target levels of phosphorus, calcium, and parathyroid hormone and developing clinical approaches that will promote parathyroid glands, bone, and cardiac health.