(See also Overview of Disorders of Phosphate Concentration.)
The usual cause of hyperphosphatemia is
Advanced renal insufficiency (glomerular filtration rate [GFR] < 30 mL/minute) reduces excretion sufficiently to increase serum phosphate. Defects in renal excretion of phosphate in the absence of chronic kidney disease also occur in pseudohypoparathyroidism, hypoparathyroidism, and parathyroid suppression (as from hypercalcemia due to vitamin A or D excess or granulomatous disease).
Hyperphosphatemia occasionally results from a transcellular shift of phosphate into the extracellular space that is so large that the renal excretory capacity is overwhelmed. This transcellular shift occurs most frequently in
Hyperphosphatemia can also occur with excessive oral phosphate administration and occasionally with overzealous use of enemas containing phosphate.
Hyperphosphatemia plays a critical role in the development of secondary hyperparathyroidism and renal osteodystrophy in patients with advanced chronic kidney disease as well as in patients on dialysis.
Hyperphosphatemia can lead to calcium precipitation into soft tissues, especially when the serum calcium × phosphate product is chronically > 55 mg2/dL2 (4.4 mmol2/L2) in patients with chronic kidney disease. Soft-tissue calcification in the skin is one cause of excessive pruritis in patients with end-stage renal disease who are on chronic dialysis. Vascular calcification also occurs in dialysis patients with a chronically elevated calcium × phosphate product; this vascular calcification is a major risk factor for cardiovascular morbidity including stroke, myocardial infarction, and claudication.
Most patients with hyperphosphatemia are asymptomatic, although symptoms of hypocalcemia, including tetany, can occur when concomitant hypocalcemia is present. Soft-tissue calcifications are common among patients with chronic kidney disease; they manifest as easily palpable, hard, subcutaneous nodules often with overlying scratches. Imaging studies frequently show vascular calcifications lining major arteries.
Hyperphosphatemia is diagnosed by phosphate concentration. When the etiology is not obvious (eg, rhabdomyolysis, tumor lysis syndrome, renal failure, overingestion of phosphate-containing laxatives), additional evaluation is warranted to exclude hypoparathyroidism or pseudohypoparathyroidism, which is end-organ resistance to parathyroid hormone (PTH). False elevation of serum phosphate also should be excluded by measuring serum protein, lipid, and bilirubin concentrations.
The mainstay of treatment in patients with advanced chronic kidney disease is reduction of phosphate intake, which is usually accomplished with avoidance of foods containing high amounts of phosphate and with use of phosphate-binding drugs taken with meals. Although quite effective, aluminum-containing antacids should not be used as phosphate binding agents in patients with end-stage renal disease because of the possibility of aluminum-related dementia and osteomalacia.
Calcium carbonate and calcium acetate are frequently used as phosphate binders. But their use requires close monitoring because of the possibility of excessive calcium × phosphate product causing vascular calcification in dialysis patients taking calcium-containing binders.
A phosphate-binding resin without calcium, sevelamer, is widely used in dialysis patients in doses of 800 to 2400 mg orally 3 times a day with meals. Lanthanum carbonate is another phosphate binder that lacks calcium and is used in dialysis patients. It is given in doses of 500 to 1000 mg orally 3 times a day with meals.
Sucroferric oxyhydroxide combines the need many dialysis patients have for elemental iron with phosphate binding. It is given in doses of 500 mg orally 3 times a day with meals.
Hemodialysis does remove some phosphate, but not enough to allow most patients with end-stage renal disease to avoid significant hyperphosphatemia without dietary interventions.
Saline diuresis can be used to enhance phosphate elimination in cases of acute hyperphosphatemia in patients with intact kidney function. Hemodialysis can lower phosphate levels in cases of severe acute hyperphosphatemia.
The usual cause of hyperphosphatemia is advanced renal insufficiency; hypoparathyroidism and pseudohypoparathyroidism are less common causes.
Most patients are asymptomatic, but those who also are hypocalcemic may have tetany.
Treat by restricting dietary phosphate and sometimes with phosphate binders.
Saline diuresis or hemodialysis may be needed.
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