Hypophosphatemia: Diagnosis and treatment


Hypophosphatemia is the low level of phosphorus on the bloodstream. Normal levels of phosphorus are between 2.5 to 4.5mg/dL. Hypophosphatemia (levels < 2.5mg/dL) may be present in up to 5% of hospitalized patients.

CAUSES:

Hypophosphatemia may be caused by different mechanisms, including:

Redistribution from the extracellular to the intracellular

Refeeding syndrome (alcoholism, anorexia treatment)
Respiratory alkalosis (acute)
Hungry bone syndrome

Decreased intestinal absorption

Poor oral intake
Diarrhea
Medications

Increased renal excretion

Hyperparathyroidism
Hypovitaminosis D
Polyuria (e.g. osmotic diuresis due to hyperglycemia)
Fanconi syndrome
Primary renal wasting (e.g. rickets)

Others

Renal replacement therapy
After Partial hepatectomy
After Renal transplantation

SIGNS & SYMPTOMS:

Manifestations of hypophosphatemia depend upon the severity and chronicity of the phosphate depletion. Most symptomatic patients have phosphate levels under 1mg/dL.

Hypophosphatemia can cause ATP depletion and that may cause neurological symptoms (irritability, paresthesias, delirium, seizures, coma), cardiovascular symptoms, myopathy or even rhabdomyolisis, and hematologic dysfunction (hemolysis, WBC dysfunction and platelet dysfunction).

Chronic hypophosphatemia increases bone resorption, hypercauciuria and may lead to rickets and osteomalacia.

DIAGNOSIS:

The etiology of the hypophosphatemia is usually evident  from the history.

If the history is not enough and the cause is unclear, phosphate excretion (24h urine) or the fractional excretion of filtered phosphate (FEPO4) may be measured. FEPO4 is calculated as follows: FEPO4 =  [UPO4  x  PCr x  100]  ÷  [PPO4  x  UCr]

  • An urinary phosphate excretion <100mg/24h or FEPO4 <5% indicates low phosphate excretion. Causes include increased cellular uptake and reduced intestinal absorption.
  • An urinary phosphate excretion >100mg/24h or FEPO4>5% in a hypophosphatemic patient indicates inappropriate phosphate excretion. Causes include hyperparathyroidism, hypovitaminosis D, Fanconi syndrome, rickets or primary renal wasting.

TREATMENT:

In patients with phosphate levels <2mg/dL, phosphate repletion can be used (15-20mg/kg/day or 1mmol/kg/day PO in 3-4 divided doses).  There is a commercial presentation available of potassium phosphate-sodium phosphate (tablet or powder for solution), 250mg (6mmol) per tablet or packet.

In patients with phosphate levels <1mg/dL IV phosphate should be given. The dose is 0.5mmol/kg  (max 80mmol) over 8-12 hours. The phosphate should be measured every 6 hours and oral phosphate should be given after the levels are above 1.5mg/dL.
SOURCES & FURTHER READING:

  1. Amanzadeh J, Reilly Jr RF. Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nature Clinical Practice Nephrology (2006) 2, 136-148.
  2. Subramanian R, Romesh K. Severe Hypophosphatemia: Pathophysiologic Implications, Clinical Presentations, and Treatment. Medicine: January 2000 – Volume 79 – Issue 1 – ppg 1-8.
  3. Geerse DA et al. Treatment of hypophosphatemia in the intensive care unit: a review. Critical Care 2010 14:R147