What causes hyperphosphatemia?

Causes of Hyperphosphatemia

The primary cause of hyperphosphatemia is chronic kidney disease (CKD), particularly in advanced stages, as the kidneys lose their ability to excrete excess phosphate. 1

Pathophysiological Mechanisms of Hyperphosphatemia

Hyperphosphatemia can result from three main mechanisms:

1. Impaired Renal Excretion:

   • Chronic kidney disease (stages G3a-G5D)
   • Acute kidney injury
   • End-stage renal disease requiring dialysis

2. Increased Phosphate Load:

   • Excessive dietary intake of phosphate (especially from processed foods with phosphate additives)
   • Excessive vitamin D supplementation
   • Rhabdomyolysis (release of phosphate from damaged muscle cells)
   • Tumor lysis syndrome
   • Phosphate-containing medications or enemas

3. Transcellular Shift:

   • Metabolic or respiratory acidosis
   • Diabetic ketoacidosis
   • Cellular breakdown (hemolysis, rhabdomyolysis)

Clinical Significance of Hyperphosphatemia

Hyperphosphatemia is not merely a laboratory abnormality but has significant clinical consequences:

• Increased mortality risk in CKD patients with phosphate levels above normal range 1
• Vascular calcification due to direct calcifying effect on vascular smooth muscle cells 1
• Cardiac disease from calcification of coronary arteries, cardiac valves, and pulmonary tissues 1
• Secondary hyperparathyroidism through:
  • Lowering ionized calcium levels
  • Interfering with 1,25(OH)₂ vitamin D production
  • Direct effects on parathyroid hormone secretion 1
• Bone disorders as part of CKD-mineral and bone disorder (CKD-MBD) 1

Diagnostic Approach to Hyperphosphatemia

When evaluating elevated phosphate levels, consider:

1. Kidney function assessment:

   • eGFR measurement to determine CKD stage
   • Urine output evaluation

2. Evaluation for modifiable factors:

   • Dietary phosphate intake (especially processed foods)
   • Vitamin D status
   • Calcium levels
   • Parathyroid hormone levels 2

3. Medication review:

   • Phosphate-containing medications
   • Vitamin D supplements
   • Phosphate binders

Management Considerations

Management should focus on treating the underlying cause:

• For CKD patients:

  • Dietary phosphate restriction (800-1,000 mg/day)
  • Phosphate binders when serum phosphate is persistently elevated
  • Increased dialytic removal for patients on dialysis 2

• For acute causes:

  • Treat the underlying condition (e.g., rhabdomyolysis, tumor lysis syndrome)
  • Consider acute dialysis for severe cases with symptoms

Important Caveats and Pitfalls

• Normal phosphate levels vary by laboratory but typically range from 2.5-4.5 mg/dL
• Target phosphate levels differ by CKD stage:
  • CKD stages 3-4: 2.7-4.6 mg/dL
  • CKD stage 5/Dialysis: 3.5-5.5 mg/dL 1, 2
• Phosphate binders should not be started for prevention in normophosphatemic patients with CKD, as this may increase coronary calcification 1
• Calcium-based phosphate binders should be restricted due to risk of hypercalcemia and vascular calcification 2
• Dietary phosphate sources vary in bioavailability:
  • Animal-based: 40-60% absorption
  • Plant-based: 20-50% absorption
  • Inorganic phosphate additives: highest bioavailability 2

Understanding the cause of hyperphosphatemia is essential for appropriate management and prevention of associated complications, particularly cardiovascular morbidity and mortality in patients with CKD.