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Hyperphosphatemia

by James L. Lewis, III, MD

Hyperphosphatemia is serum phosphate (PO 4 ) concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical features may be due to accompanying hypocalcemia and include tetany. Diagnosis is by serum PO 4 . Treatment includes restriction of PO 4 intake and administration of PO 4 binding antacids, such as Ca carbonate.

The usual cause of hyperphosphatemia is a decrease in renal excretion of PO 4 . Advanced renal insufficiency (GFR < 30 mL/min) reduces excretion sufficiently to increase serum PO 4 . Defects in renal excretion of PO 4 in the absence of renal failure also occur in pseudohypoparathyroidism and hypoparathyroidism. Hyperphosphatemia can also occur with excessive oral PO 4 administration and occasionally with overzealous use of enemas containing PO 4 .

Hyperphosphatemia occasionally results from a transcellular shift of PO 4 into the extracellular space that is so large that the renal excretory capacity is overwhelmed. This transcellular shift occurs most frequently in diabetic ketoacidosis (despite total body PO 4 depletion), crush injuries, and nontraumatic rhabdomyolysis as well as in overwhelming systemic infections and tumor lysis syndrome.

Major causes of hyperphosphatemia include

  • GFR < 30 mL/min

  • Hypoparathyroidism

  • Pseudohypoparathyroidism

  • Excessive oral PO 4 administration

  • Overzealous use of enemas containing PO 4

  • Shifts of PO 4 into the extracellular space (eg, in diabetic ketoacidosis, rhabdomyolysis, overwhelming systemic infections, and tumor lysis syndrome)

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. Lastly, hyperphosphatemia can be spurious in cases of hyperproteinemia (multiple myeloma or Waldenström macroglobulinemia), hyperlipidemia, hemolysis, or hyperbilirubinemia.

Hyperphosphatemia can lead to Ca precipitation into soft tissues, especially when the serum Ca × PO 4 product is chronically > 55 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 on chronic dialysis. Vascular calcification also occurs in dialysis patients with a chronically elevated Ca x PO 4 product; this vascular calcification is a major risk factor for cardiovascular morbidity including stroke, MI, and claudication.

Symptoms and Signs

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.

Diagnosis

  • PO 4 concentration > 4.5 mg/dL (> 1.46 mmol/L)

Hyperphosphatemia is diagnosed by PO 4 concentration. When the etiology is not obvious (eg, rhabdomyolysis, tumor lysis syndrome, renal failure, overingestion of PO 4 containing laxatives), additional evaluation is warranted to exclude hypoparathyroidism or pseudohypoparathyroidism, which is end-organ resistance to parathyroid hormone (PTH—see Pseudohypoparathyroidism). False elevation of serum PO 4 also should be excluded by measuring serum protein, lipid, and bilirubin concentrations.

Treatment

  • PO 4 restriction

  • PO 4 binders

The mainstay of treatment in patients with renal failure is reduction of PO 4 intake, which is usually accomplished with avoidance of foods containing high amounts of PO 4 and with use of PO 4 binding drugs taken with meals. Because of the possibility of aluminum-related osteomalacia, Ca carbonate and Ca acetate replace aluminum-containing antacids in patients with end-stage renal disease. Because of the possibility of excessive Ca × PO 4 product causing vascular calcification in dialysis patients taking Ca-containing binders, a PO 4 binding resin without Ca, sevelamer, is widely used in dialysis patients in doses of 800 to 2400 mg po tid with meals. Lanthanum carbonate, another PO 4 binder that lacks Ca, can also be used in dialysis patients. It is given in doses of 500 to 1000 mg po tid with meals.

Key Points

  • The usual cause of hyperphosphatemia is advanced renal insufficiency; pseudohypoparathyroidism and hypoparathyroidism are less common causes.

  • Most patients are asymptomatic, but those who also are hypocalcemic may have tetany.

  • Treat by restricting dietary PO 4 and sometimes with PO 4 binders.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • RENAGEL
  • FOSRENOL

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