HyperPhosphatemia

Question 1

Causes of Hyperphosphatemia

Answer 1

Pseudohyperphosphatemia:

1. Heparin-containing blood samples due to phosphate-containing preservatives
2. Paraproteinemia (multiple myeloma) if phosphate is measured with the phosphomolybdate ultraviolet assay

Question 2

Causes of Hyperphosphatemia

Answer 2

Exogenous sources (usually in association with poor kidney function and excretion):

1. Excessive ingestion of phosphate salts, for example, accidental ingestion of phosphate-containing enemas
2. Treatment with vitamin D (increase GI absorption of phosphates)

Question 3

Causes of Hyperphosphatemia

Answer 3

Extracellular shift:

Cell death, extracellular release of phosphate: rhabdomyolysis, hemolysis, malignant hyperthermia, heavy tumor burden with necrotic cell death, tumor lysis syndrome, bowel infarction

Question 4

Causes of Hyperphosphatemia

Extracellular shift:

Answer 4

Acid–base status:

a. Lactic acidosis
b. Diabetic ketoacidosis
c. Chronic respiratory alkalosis (associated with prolonged hyperventilation) may lead to renal resistance to PTH, hyperphosphatemia, hypocalcemia, and possibly reduced PTH secretion.

Question 5

Causes of Hyperphosphatemia

Extracellular shift:

Reduced kidney excretion:

Answer 5

Reduced kidney excretion:

a. Reduced kidney function (typically with GFR < 25 to 30 mL/min/1.73 m2)
b. Hypoparathyroidism (idiopathic, postsurgical, pseudohypoparathyroidism, PTH resistance, abnormal forms of plasma PTH)
c. Drug-induced: bisphosphonates

Question 6

Causes of Hyperphosphatemia

Extracellular shift:

Reduced kidney excretion:

Answer 6

d. Acromegaly: Increased growth hormone and insulin-like growth factor-1 in acromegaly can increase tubular reabsorption of phosphate.

Question 7

Causes of Hyperphosphatemia

Extracellular shift:

Reduced kidney excretion:

Answer 7

e. Familial tumoral calcinosis:
1. Rare autosomal recessive disorder affecting Middle Eastern or African ancestries
2. Thought to involve inactivating mutations of GALnt3, FGF-23, or klotho genes, all of which are necessary for optimal FGF-23 activity. (GALnt3 codes for glycosyltransferase, an enzyme necessary for post-translational processing and stabilization of FGF-23.)

Question 8

Causes of Hyperphosphatemia

Extracellular shift:

Reduced kidney excretion:

Answer 8

3. The lack of active FGF-23 (low FGF-23) leads to the following:
   a. Hyperphosphatemia
   b. Loss of FGF-23 inhibitory effect on 1,25 vitamin D synthesis → elevated 1,25 vitamin D (increased GI calcium absorption) → low PTH → hypercalciuria
   c. Normal SCa due to opposing effects of 1,25 vitamin D and PTH
   d. Ectopic calcifications due to combination of positive calcium balance and hyperphosphatemia

Question 9

Management of Hyperphosphatemia

Answer 9

Dietary restriction

Fluid resuscitation to ensure good renal excretion

Phosphate binders with meals to reduce GI absorption (See Secondary Hyperparathyroidism)

Intravenous dextrose and insulin to increase intracellular phosphate shift