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Hyperphosphatemia is serum phosphate (PO4) 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 PO4. Treatment includes restriction of PO4 intake and administration of PO4 binding antacids, such as Ca carbonate.
The usual cause of hyperphosphatemia is a decrease in renal excretion of PO4. Advanced renal insufficiency (GFR < 30 mL/min) reduces excretion sufficiently to increase serum PO4. Defects in renal excretion of PO4 in the absence of renal failure also occur in pseudohypoparathyroidism and hypoparathyroidism. Hyperphosphatemia can also occur with excessive oral PO4 administration and occasionally with overzealous use of enemas containing PO4.
Hyperphosphatemia occasionally results from a transcellular shift of PO4 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 PO4 depletion), crush injuries, and nontraumatic rhabdomyolysis as well as in overwhelming systemic infections and tumor lysis syndrome.
Major causes of hyperphosphatemia include
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 × PO4 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 PO4 product; this vascular calcification is a major risk factor for cardiovascular morbidity including stroke, MI, 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 PO4 concentration. When the etiology is not obvious (eg, rhabdomyolysis, tumor lysis syndrome, renal failure, overingestion of PO4 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 PO4 also should be excluded by measuring serum protein, lipid, and bilirubin concentrations.
The mainstay of treatment in patients with renal failure is reduction of PO4 intake, which is usually accomplished with avoidance of foods containing high amounts of PO4 and with use of PO4 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 × PO4 product causing vascular calcification in dialysis patients taking Ca-containing binders, a PO4 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 PO4 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.
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