Disorders of Phosphate Metabolism

Question 1

DISORDERS OF PHOSPHATE METABOLISM

Phosphate Background

Answer 1

99% of total body phosphates (700 g) exist intracellularly and in bones.

1% of total body phosphates exist extracellularly as HPO42− and H2PO4− in a 4:1 ratio, with normal serum phosphate concentrations of 2.8 to 4.5 mg/dL.

Question 2

DISORDERS OF PHOSPHATE METABOLISM

Phosphate Background

Answer 2

Daily phosphate intake is ~1 to 1.5 g/d, where 60% to 80% is absorbed by the GI tract and 10% is secreted back into the GI tract.

Kidney excretes 60% to 70% of dietary intake.

Question 3

DISORDERS OF PHOSPHATE METABOLISM

Phosphate Background

Answer 3

Less than 1% of total body phosphate is involved in constant bone turnover.

Physiologic roles of phosphate: bone mineralization, phospholipid bilayers, ATP, DNA/RNA synthesis, glycolysis, cell function, unloading of O2 via 2,3-bisphoglycerate

Question 4

Phosphate Metabolism

Answer 4

Gastrointestines:

GI phosphate absorption is linear and nonsaturable function of phosphate intake.

Absorption ccurs via both paracellular and transcellular pathways.

Question 5

Phosphate Metabolism

Answer 5

Transcellular absorption occurs via sodium–phosphate (Na-Pi) cotransporters, type 2b in the small intestines.

a. NPT2b, the gene encoding Na-Pi 2b, is upregulated by calcitriol.
b. Niacin inhibits Na-Pi 2b and has been used to reduce GI phosphate absorption. Niacin may reduce phosphate by 0.4 mg/dL.
c. Deletion of NPT2b has no phosphate phenotype in humans. It is possible that paracellular absorption alone may be sufficient to maintain phosphate levels.

Question 6

Phosphate Metabolism

Kidney

Answer 6

Kidney:

Phosphate is minimally protein bound and freely filtered in the glomeruli.

Total renal reabsorption is approximately 80% to 95%, leaving fractional excretion of phosphate (FEPO4) to be 5% to 20%.

Question 7

Phosphate Metabolism

Kidney

Proximal Tubules

Answer 7

Proximal tubules:

Absorption of phosphate occurs via Na-Pi, types 2a and 2c, at the brush borders of proximal tubules.

FGF-23 and PTH downregulates NPT2a (gene encoding Na-Pi 2a), thus enhances phosphaturia.

Question 8

Phosphate Metabolism

Kidney

Proximal Tubules

Answer 8

NOTE: For optimal FGF-23 binding and function in the kidneys, FGF-23 requires the cofactor klotho. Mutations of either FGF-23 or klotho can reduce phosphaturia.

Typically, kidneys excrete 5% to 20% of filtered phosphate load to maintain phosphate balance, that is FEPO4 is 5% to 20%.

Question 9

Phosphate Metabolism

Kidney

Proximal Tubules

Answer 9

In CKD, when GFR is reduced, each of the remnant nephrons will have to reabsorb more phosphate per filtered load to maintain balance. FEPO4 can exceed 50%.

Question 10

Phosphate Metabolism

Kidney

Proximal Tubules

Answer 10

FEPO4 = (UPO4 × SCr)/(SPO4 × UCr),

where UPO4 = urine phosphate concentration

SCr = serum creatinine

SPO4 = serum phosphate concentration

UCr = urine creatinine concentration

NOTE: This is similar to the calculation of FeNa.