Hyperphosphataemia is defined as a serum phosphate concentration > 1.5 mmol/L.
Hyperphosphataemia is commonly observed in patients with chronic kidney disease (CKD) because regulation of dietary phosphate is primarily by renal excretion.
The normal plasma concentration of phosphate is 0.8-1.5 mmol/L. Hyperphosphataemia is defined by an elevated phosphate level >1.5 mmol/L. It predominantly occurs when dietary intake of phosphate exceeds renal excretion, but may also occur with massive cell lysis. This is because phosphate is predominantly an intracellular ion.
The human body contains approximately 1000 g of phosphate of which 80-90% is found in bone.
Phosphate is an essential ion for formation of nucleic acids, normal cellular function and bone mineralisation. The addition (by a kinase) or removal (by a phosphatase) of a phosphate molecule is important for the regulation of enzymes
Approximately 1000 g of phosphate is contained within the human body, which is distributed between different structures:
Therefore, the concentration of serum phosphate does not reflect the proportion of total body phosphate.
Our normal daily intake of phosphate is 800-1500 mg. Most foods contain phosphate and the majority is absorbed from the gastrointestinal tract (70-90%) with the remaining being excreted in faeces.
The absorption of phosphate, which predominantly occurs in the small intestines, may be blocked by aluminum-/calcium-/magnesium-containing antacids. This forms the basis of therapy in CKD.
Phosphate is predominantly an intracellular ion with only 1% composing the extracellular pool. This extracellular concentration is closely regulated by diet, hormones (e.g. parathyroid hormone) and acid-balance.
Excess phosphate can be excreted by the kidneys in the proximal and distal convoluted tubules. The proximal convoluted tubule may also reabsorb phosphate in the context of low levels via a sodium phosphate cotransporter. The principle regulators of this process are vitamin D and parathyroid hormone (PTH).
PTH also leads to bone resorption, which leads to an increase in extracellular phosphate and calcium. In normal renal function, the increased inhibition of phosphate reabsorption causes a net loss of phosphate. However, in the context of renal impairment the bone resorption causes a net gain of phosphate leading to chronic hyperphosphataemia.
Other molecules more recently discovered to play a role in phosphate regulation include fibroblast growth factor 23(FGF23), phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and stanniocalcin.
Chronic kidney disease is an extremely common cause of hyperphosphataemia.
Hyperphosphataemia develops by four main mechanisms:
An acute rise in phosphate is commonly due to exogenous administration (usually in context of impaired renal function) or from massive cell destruction leading to release of phosphate.
Exogenous administration is typically seen with the use of phosphate-containing laxatives.
Massive cell destruction or lysis leading to release of phosphate is seen in two major conditions
Hyperphosphataemia is usually seen when the estimated glomerular filtration rate falls below 25 ml/min (CKD stage 4). At this stage, the increase in PTH, which promotes phosphate excretion, can no longer maintain normal phosphate balance as phosphate reabsorption is maximally suppressed.
For more information, see our notes on Chronic kidney disease.
The majority of patients with hyperphosphataemia are asymptomatic.
The clinical features in hyperphosphataemia may reflect the underlying cause. For example, lethargy, weakness, nausea and anorexia is seen in renal disease.
If symptoms are present, they are usually due to hypocalcaemia. This is because high levels of phosphate results in binding to serum calcium leading to a fall in free ionised calcium.
This usually occurs at calcium concentrations < 1.9 mmol/L
Two classical eponymous signs are associated with hypocalcaemia:
* Carpopedal spasm refers to flexion at the wrist and metacarpophalangeal joints, extension of the interphalangeal joints and adduction of the thumb
The diagnosis of hyperphosphataemia is based on a serum phosphate >1.5 mmol/L.
A bone profile will identify the elevated phosphate level and this is regularly monitored in patients with CKD. Other blood tests may be useful to determine the underlying cause, which include:
Acute hyperphosphataemia and subsequent secondary hypocalcaemia can be life-threatening.
Acute hyperphosphataemia (e.g. tumour lysis syndrome), usually resolves within 6-12 hours in the context of normal renal function if the offending cause is removed. Intravenous sodium chloride can be administered to enhance phosphate excretion.
Chronic hyperphosphataemia that requires treatment generally only occurs in the context of CKD or rare inherited disorders.
The management of hyperphosphataemia depends on the degree of renal impairment and treatment usually following the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines
Hyperphosphataemia can be associated with both short and long-term complications.
These complications usually occur from secondary hypocalcaemia
Chronic hyperphosphataemia is associated with accelerated vascular calcification, which can lead to organ damage. In patients with CKD it is an independent risk factor for cardiovascular disease.
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