Regulation of Phosphate in Health and Disease*

As is true of many physiologically critical systems, phosphate metabolism is a highly regulated process. The traditional view of hormonal control of the physicochemical relationship between minerals and tissues has given way to an expanding view of elaborate, active processes that bridge multiple organ systems. The impact of early changes in mineral metabolism that accompany loss of renal function in chronic kidney disease (CKD) may be more important to cardiovascular complications of CKD than previously thought. An understanding of these metabolic processes is critical to treating hyperphosphatemia and to preventing the serious consequences of this common complication of CKD. (Adv Stud Med. 2007;7(5):133-139) M ineral metabolism is modulated by complex neuroendocrine interactions involving multiple organ systems. Calcium and phosphorus homeostasis is maintained through a combination of effects on kidney and bone orchestrated by parathyroid hormone (PTH). In the kidney, PTH modulates calcium and phosphorus reabsorption and excretion. In bone, PTH regulates turnover of these minerals. Serum mineral concentrations reflect dietary intake as well as the actions of PTH, vitamin D, and other hormones. In patients with chronic kidney disease (CKD), the progressive loss of renal function is uniformly accompanied by altered mineral metabolism. PTH levels begin to rise as glomerular filtration rate (GFR) decreases to 60 mL/min/1.73 m2. As GFR declines and the intake of dietary phosphorus does not change, the filtered load of phosphorus ultimately also decreases. Increasing secretion of PTH appears to be an adaptive response to the need for increased fractional phosphorous excretion in order to maintain phosphorus balance. Eventually, even a state of hyperparathyroidism and other adaptive mechanisms cannot compensate for loss of kidney function, and serum phosphate levels rise beyond the physiologic range. Apart from the effects on PTH secretion and serum calcium levels, the resulting state of hyperphosphatemia is an independent risk factor for mortality in patients with stage 5 CKD. With less severe forms of renal dysfunction, incremental increases in serum phosphate levels—even within the generally accepted reference range—are associated with cardiovascular events that are, in turn, a major cause of morbidity and mortality in these patients. This article will describe the regulation of phosphate homeostasis in individuals with normal renal function and the progressive changes in phosphate PROCEEDINGS