Hyperphosphatemia in Children

Hyperphosphatemia in Children Introduction Etiology Clinical Manifestations Diagnosis Treatment Complications Prognosis

Introduction to Hyperphosphatemia in Children

Hyperphosphatemia is a metabolic disorder characterized by abnormally high levels of phosphate in the blood. In children, this condition can have significant implications for growth, development, and overall health. Phosphate is crucial for various physiological processes, including bone formation, energy metabolism, and cellular signaling.

Normal serum phosphate levels vary by age:

• Infants: 4.5-8.3 mg/dL
• Children: 4.5-6.5 mg/dL
• Adolescents: 2.7-4.7 mg/dL

Hyperphosphatemia is generally defined as serum phosphate levels above the upper limit of normal for age. Levels exceeding 7 mg/dL in children or 5 mg/dL in adolescents are considered significant hyperphosphatemia.

Etiology of Hyperphosphatemia in Children

The causes of hyperphosphatemia in children can be categorized into several mechanisms:

1. Increased phosphate intake:
   • Excessive dietary intake (rare in children with normal renal function)
   • Iatrogenic (e.g., phosphate-containing enemas, excessive IV phosphate administration)
2. Decreased renal excretion:
   • Acute kidney injury
   • Chronic kidney disease
   • Hypoparathyroidism
   • Pseudohypoparathyroidism
3. Shift of phosphate from intracellular to extracellular space:
   • Tumor lysis syndrome
   • Rhabdomyolysis
   • Hemolysis
   • Severe acidosis
4. Increased bone resorption:
   • Hypervitaminosis D
   • Metastatic bone disease (rare in children)
5. Genetic disorders:
   • Familial tumoral calcinosis
   • Hyperphosphatemic familial tumoral calcinosis (HFTC)

In children, renal dysfunction and conditions causing rapid cell breakdown (e.g., tumor lysis syndrome) are common causes of hyperphosphatemia.

Clinical Manifestations of Hyperphosphatemia in Children

The clinical presentation of hyperphosphatemia in children can vary depending on the severity, duration, and underlying cause:

• Acute hyperphosphatemia:
  • Often asymptomatic if mild to moderate
  • Nausea and vomiting
  • Diarrhea
• Chronic hyperphosphatemia:
  • Metastatic calcifications in soft tissues
  • Pruritus
  • Bone and joint pain
  • Growth retardation
• Secondary hypocalcemia manifestations:
  • Muscle cramps
  • Tetany
  • Seizures (in severe cases)
• Cardiovascular manifestations:
  • Hypertension
  • Vascular calcifications (in chronic cases)
• Renal manifestations:
  • Nephrocalcinosis
  • Kidney stones

In chronic kidney disease, hyperphosphatemia contributes to mineral and bone disorder (CKD-MBD), affecting bone metabolism and growth in children.

Diagnosis of Hyperphosphatemia in Children

Diagnosis of hyperphosphatemia involves a combination of clinical assessment, laboratory tests, and imaging studies:

1. Laboratory tests:
   • Serum phosphate levels
   • Serum calcium and ionized calcium levels
   • Parathyroid hormone (PTH) levels
   • Vitamin D levels (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D)
   • Renal function tests (BUN, creatinine, eGFR)
   • Urinary phosphate excretion
   • Serum uric acid (in cases of suspected tumor lysis syndrome)
2. Imaging studies:
   • X-rays to detect soft tissue calcifications
   • Renal ultrasound for nephrocalcinosis or kidney stones
   • Bone density scans in chronic cases
3. Additional tests:
   • Genetic testing for suspected familial disorders
   • Fibroblast growth factor 23 (FGF23) levels in certain cases

The fractional excretion of phosphate (FEPi) can help differentiate between renal and non-renal causes of hyperphosphatemia. A low FEPi in the presence of hyperphosphatemia suggests impaired renal phosphate excretion.

Treatment of Hyperphosphatemia in Children

The treatment approach for hyperphosphatemia in children depends on the underlying cause, severity, and associated complications:

1. Acute management:
   • Treat underlying cause (e.g., tumor lysis syndrome, rhabdomyolysis)
   • Increase renal phosphate excretion:
     • IV fluids to enhance phosphate clearance
     • Loop diuretics in some cases
   • Phosphate binders for severe cases:
     • Calcium-based binders (e.g., calcium carbonate) if calcium levels are not elevated
     • Non-calcium-based binders (e.g., sevelamer) if hypercalcemia is present
2. Chronic management:
   • Dietary phosphate restriction:
     • Limit high-phosphate foods
     • Educate on hidden phosphate sources in processed foods
   • Phosphate binders with meals
   • Treatment of underlying conditions (e.g., management of chronic kidney disease)
3. Specific treatments:
   • Dialysis in severe cases or refractory hyperphosphatemia
   • Calcimimetics (e.g., cinacalcet) in secondary hyperparathyroidism
   • Vitamin D analogs in hypoparathyroidism

Regular monitoring of serum phosphate, calcium, PTH, and renal function is essential during treatment. In growing children, monitoring of growth and bone health is crucial.

Complications of Hyperphosphatemia in Children

Untreated or poorly managed hyperphosphatemia can lead to several complications:

• Cardiovascular:
  • Vascular calcifications
  • Increased cardiovascular morbidity and mortality (especially in CKD)
• Renal:
  • Nephrocalcinosis
  • Kidney stones
  • Progression of chronic kidney disease
• Skeletal:
  • Renal osteodystrophy in CKD
  • Growth retardation
  • Bone deformities
• Endocrine:
  • Secondary hyperparathyroidism
  • Tertiary hyperparathyroidism in long-standing cases
• Soft tissue:
  • Metastatic calcifications
  • Calciphylaxis (rare in children)
• Neuromuscular:
  • Muscle weakness due to associated hypocalcemia

Long-term complications can significantly impact quality of life and may lead to increased morbidity and mortality, particularly in children with chronic kidney disease.

Prognosis of Hyperphosphatemia in Children

The prognosis for children with hyperphosphatemia varies depending on the underlying cause, severity, and timeliness of treatment:

• Acute, transient hyperphosphatemia: Generally good prognosis with prompt treatment
• Chronic hyperphosphatemia:
  • Associated with chronic kidney disease: Prognosis depends on the management of CKD and associated complications
  • Genetic causes: May require lifelong management, but outcomes can be improved with early diagnosis and treatment
  • Secondary to other disorders: Prognosis depends on the underlying condition

Factors influencing prognosis:

• Age at diagnosis and initiation of treatment
• Adherence to dietary restrictions and medication regimens
• Presence and severity of complications at diagnosis
• Response to therapy
• Management of underlying conditions (e.g., CKD progression)

With appropriate management, many children with hyperphosphatemia can achieve improved outcomes. However, those with chronic conditions may face long-term challenges related to growth, bone health, and cardiovascular risk. Regular follow-up and a multidisciplinary approach are essential for optimizing outcomes in these patients.

Hyperphosphatemia in Children

1. What is the definition of hyperphosphatemia in children?
   Serum phosphate levels above the age-specific normal range
2. What is the normal range of serum phosphate levels in infants (0-1 year)?
   4.8-7.4 mg/dL (1.55-2.39 mmol/L)
3. What is the normal range of serum phosphate levels in children (1-12 years)?
   3.7-5.6 mg/dL (1.19-1.81 mmol/L)
4. Which organ plays the primary role in regulating phosphate levels in the body?
   Kidneys
5. What hormone is responsible for increasing phosphate excretion in the kidneys?
   Parathyroid hormone (PTH)
6. Which vitamin is essential for proper phosphate absorption in the intestines?
   Vitamin D
7. What is the most common cause of hyperphosphatemia in children with normal kidney function?
   Excessive intake of phosphate (dietary or iatrogenic)
8. Which electrolyte imbalance is commonly associated with hyperphosphatemia?
   Hypocalcemia
9. What is the primary mechanism by which chronic kidney disease causes hyperphosphatemia?
   Decreased phosphate excretion
10. Which condition can cause rapid cell lysis, leading to acute hyperphosphatemia?
    Tumor lysis syndrome
11. What is the role of fibroblast growth factor 23 (FGF23) in phosphate regulation?
    Promoting phosphate excretion and inhibiting vitamin D activation
12. Which endocrine disorder can cause hyperphosphatemia due to decreased PTH levels?
    Hypoparathyroidism
13. What is the primary goal of treatment for hyperphosphatemia?
    Lowering serum phosphate levels to the normal range
14. Which medication class is commonly used to bind phosphate in the gastrointestinal tract?
    Phosphate binders
15. What is the mechanism of action of calcium-based phosphate binders?
    Forming insoluble calcium-phosphate complexes in the intestine
16. Which non-calcium-based phosphate binder is commonly used in children with chronic kidney disease?
    Sevelamer
17. What dietary modification is typically recommended for children with hyperphosphatemia?
    Restriction of phosphate-rich foods
18. Which phosphate-rich foods should be limited in children with hyperphosphatemia?
    Dairy products, nuts, beans, and processed foods
19. What is the role of dialysis in managing hyperphosphatemia in children with end-stage renal disease?
    Removing excess phosphate from the blood
20. Which complication of hyperphosphatemia can lead to soft tissue calcifications?
    Metastatic calcification
21. What is the term for abnormal calcium-phosphate deposition in blood vessels and soft tissues?
    Calciphylaxis
22. Which bone disorder is associated with chronic hyperphosphatemia in children with kidney disease?
    Renal osteodystrophy
23. What is the primary mechanism by which hyperphosphatemia leads to secondary hyperparathyroidism?
    Decreased calcium levels stimulating PTH secretion
24. Which imaging technique is commonly used to assess vascular calcifications in children with chronic hyperphosphatemia?
    Computed tomography (CT)
25. What is the calcium-phosphate product, and why is it important in hyperphosphatemia management?
    The product of serum calcium and phosphate levels; elevated levels increase the risk of tissue calcification
26. Which medication used in the treatment of seizures can cause iatrogenic hyperphosphatemia?
    Phosphate-containing enemas
27. What is the role of growth hormone in phosphate regulation during childhood?
    Promoting phosphate reabsorption in the kidneys
28. Which genetic disorder is characterized by hyperphosphatemia and elevated FGF23 levels?
    Familial tumoral calcinosis
29. What is the primary cause of hyperphosphatemia in children with rhabdomyolysis?
    Release of phosphate from damaged muscle cells
30. Which laboratory test is used to assess the body's ability to excrete phosphate?
    Fractional excretion of phosphate (FEPi)

Further Reading

• Hyperphosphatemia - StatPearls
• Clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) - Kidney International
• Management of Hyperphosphatemia in Pediatric Chronic Kidney Disease - Pediatric Nephrology
• Hyperphosphatemia in children: pathophysiology, management, and treatment - Clinical Kidney Journal