What causes hyperphosphatemia?

Causes of Hyperphosphatemia

Hyperphosphatemia is primarily caused by impaired renal phosphate excretion due to chronic kidney disease (CKD), with additional causes including cell lysis conditions, endocrine disorders, and excessive phosphate intake or administration. 1

Pathophysiological Mechanisms

Kidney Disease-Related Causes

• Chronic Kidney Disease: The most common cause of chronic hyperphosphatemia
  • Phosphate retention begins early in CKD (Stage 1) but serum levels typically remain normal until GFR falls below 20-30 mL/min/1.73m² (CKD Stage 4) 1
  • Early compensatory mechanisms include increased PTH secretion and decreased tubular reabsorption of phosphate 1
  • As kidney function declines, these compensatory mechanisms fail, leading to hyperphosphatemia 2

Acute Causes

• Cell Lysis Syndromes: Release intracellular phosphate into circulation 1
  • Tumor lysis syndrome
  • Rhabdomyolysis
  • Hemolysis
  • Severe catabolic states

Endocrine Disorders

• Hypoparathyroidism: Decreased PTH leads to increased renal phosphate reabsorption 1
• Pseudohypoparathyroidism: End-organ resistance to PTH 1
• Acromegaly: Growth hormone excess increases phosphate reabsorption 1

Exogenous Sources

• Excessive Dietary Intake: Particularly from processed foods with phosphate additives 2, 3
  • Average intake is now about twice the recommended dietary allowance 3
  • High protein diets combined with elevated PTH significantly increase hyperphosphatemia risk 4
• Phosphate-Containing Medications: Laxatives, enemas, vitamin D supplements 1
• Parenteral Administration: Phosphate-containing solutions 1

Contributing Factors

Vitamin D Metabolism

• Decreased production of 1,25-dihydroxycholecalciferol (active vitamin D) in CKD contributes to secondary hyperparathyroidism 2, 1
• Decreased vitamin D receptors in parathyroid glands increases resistance to vitamin D action 2

Calcium-Phosphate Balance

• Hyperphosphatemia directly decreases ionized calcium levels, stimulating PTH release 2
• Calcium-phosphate product may precipitate in tissues, leading to ectopic calcification 5

Secondary Hyperparathyroidism

• Develops as a compensatory response to maintain phosphate homeostasis 2, 1
• Contributes to bone disease and mineral metabolism disorders 2
• High PTH combined with high protein intake creates a threefold higher risk of hyperphosphatemia 4

Diagnostic Evaluation

Laboratory Assessment

• Comprehensive metabolic panel including creatinine, eGFR, calcium, potassium, uric acid, and LDH 1
• PTH and 25-OH vitamin D levels to assess hyperparathyroidism and vitamin D status 1
• Serum bicarbonate levels to evaluate metabolic acidosis 1

Imaging

• Renal ultrasound to evaluate kidney size, morphology, and possible obstructions 1
• Bone densitometry and radiographs to evaluate for renal osteodystrophy 1

Clinical Implications

Hyperphosphatemia is associated with:

• Increased cardiovascular morbidity and mortality 6, 7
• Vascular and soft tissue calcification 6
• Bone mineral disorders 1
• Progression of kidney disease 3

Early recognition and management of hyperphosphatemia is critical to prevent these complications, particularly in patients with CKD where it represents a modifiable risk factor for disease progression and cardiovascular events.