Hyperphosphatemia is a condition characterized by elevated levels of phosphate in the blood. Under normal conditions phosphate is used to construct bones and cell membranes, as well as a coenzyme that regulates intracellular enzymes. Phosphate levels in the blood are carefully regulated by vitamin D and parathyroid hormone.
Signs and symptoms associated with acute hyperphosphatemia are caused by hypocalcemia and include:
However, some symptoms are considered to be exclusively caused by elevated levels of phosphate ions. Cataracts can be attributed to hyperphosphatemia. Additionally, cardiovascular and nervous system dysfunction results in hypotension, prolonged QT syndrome, delirium, and possibly coma.
Entire Body System
Ferric Citrate May Lessen Anemia in Advanced CKD The phosphate binder ferric citrate coordination complex may mitigate anemia, elevated phosphorus, and FGF23 in patients with advanced CKD, new research suggests. Next post in Hyperphosphatemia [renalandurologynews.com]
Sucroferric oxyhydroxide and ferric citrate are calcium-free and may offer benefits in those with a high pill burden and in patients with concurrent anemia, respectively. [creighton.pure.elsevier.com]
Anemia and hyperphosphatemia in ESRD In patients with ESRD and kidney transplant recipients, a previous study [ 6 ] found a relationship between hyperphosphatemia and anemia. [bmcnephrol.biomedcentral.com]
[…] bone resorption Transcellular shift from intracellular to extracellular spaces Catabolic states Fulminant hepatitis Hyperthermia Rhabdomyolysis—crush injuries or nontraumatic Cytotoxic therapy—tumor lysis Acute leukemia Diabetic ketoacidosis Hemolytic anemia [accessmedicine.mhmedical.com]
Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013;28(8):1793-1803.PubMedGoogle ScholarCrossref [jamanetwork.com]
“By embedding rigorous research into clinical care delivery, HiLo addresses a question of great importance to patients and clinicians,” according to the University of Pennsylvania’s Laura Dember, MD, a member of the HiLo Steering Committee. [dcri.org]
Furthermore, elevated phosphorus levels can cause bone loss, decreased bone density, fibrosis and bone fractures. [checkorphan.org]
[…] heart rate Muscle spasm, followed by numbness and pain Muscle weakness Numbness and tingling around mouth and fingertips Anorexia Nausea and vomiting Formation of calcium phosphate in tissues, joints, and arteries with prolonged hyperphosphatemia Bone fractures [consultant360.com]
With continuous high blood phosphorus concentration, the risk of renal osteodystrophy characterized by a high tendency of bone pain and bone fracture is known to be increased. [astellas.com]
One should ask about previously diagnosed bone disorders or symptoms that may hint to the underlying condition such as bone pain, change in ring size/hat size, vertebral fractures or other long bone fractures. [cancertherapyadvisor.com]
Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. [ncbi.nlm.nih.gov]
Slatopolsky E, Gradowska L, Kashemsant C, Keltner R, Manley C, Bricker NS: The control of phosphate excretion in uremia. J Clin Invest 1966;45:672–677. [karger.com]
Use of the term uremia Before the advancement of modern medicine, renal failure was often referred to as uremic poisoning. Uremia was the term for the contamination of the blood with urea. [en.wikipedia.org]
Hyperphosphatemia is diagnosed by a simple blood test to measure phosphate. However, other testing is necessary to evaluate other electrolytes, kidney function, and parathyroid function. The recommended blood tests include:
- Parathyroid hormone (PTH)
- Phosphate 
- Vitamin D
Testing the urine has no role in evaluating hyperphosphatemia.
Most imaging studies are not warranted; however, metastatic calcifications can be evaluated and monitored by radiography. These calcifications can be found in the basal ganglia and periarticular joint spaces.
Secondary hyperparathyroidism due to renal failure requires long-bone studies to assess for hyperparathyroid bone disease. Densitometry is recommended in cases where excess bone loss is suspected. Coronary artery calcifications and calcifications of the peripheral vasculature can be assessed by electron beam CT. Studies suggest patients with renal failure and patients on dialysis with valvular and coronary artery calcifications have a poor outcome.
Imaging, especially bone studies and coronary calcification, can provide useful information regarding chronicity and are useful in determining the patient’s prognosis. A chronic process may show kidney shrinkage, a sign of kidney failure, and coronary calcifications.
Bone biopsy findings may be helpful to differentiate osteomalacia (bone softening due to low levels of Vitamin D, seen in adults) from parathyroid bone disease.
- Calcium Decreased
[…] levels in the body—important for cardiac function (when phosphorus increases, calcium decreases, and vice versa) Aid for gastric motility Foods containing phosphorus If you consume too much phosphorus, the kidneys normally will excrete the excess. [consultant360.com]
The decrease of active vitamin D results in decreased intestinal absorption of calcium, decreased renal calcium and phosphate reabsorption, and impaired bone mineralization. [ncbi.nlm.nih.gov]
Diagnosing and treating the underlying cause of hyperphosphatemia should be completed in parallel with restoring phosphate levels to normal. Dietary modification is a very effective method in controlling phosphate levels. Medications may also be necessary. There are two classes of drugs to control phosphate levels: phosphate binders and loop diuretics.
Phosphate binders are taken orally and neutralize phosphate ions and phosphorous in the GI tract, allowing it to bypass absorption and be excreted with the stool. These include:
Calcium Phosphate Binders
- Calcium carbonate 
- Calcium acetate 
Non Calcium Phosphate Binders
- Aluminum hydroxide
- Magnesium hydroxide
- Lanthanum carbonate
- Sevelamer hydrochloride 
In patient with end-stage renal disease there is an increased risk for aluminum-related osteomalacia. Aluminum hydroxide should not be used as a phosphate binder in this population. A physician should use calcium carbonate or calcium acetate instead. Patients on dialysis have an increased risk of vascular calcification when taking phosphate binders that contain calcium. Sevelamer is a phosphate binding resin that does not contain calcium and should be used with this population.
In patients with limited or no kidney function, phosphate can be removed during dialysis treatment. This may be the most effective method to remove phosphate from the body.
Acute hyperphosphatemia is usually an asymptomatic condition. Even a large increase in phosphate concentration in the blood rarely results in immediate clinical manifestation. Acutely, complications of hyperphosphatemia include hypocalcemia and tetany. Additionally, excessive phosphate will precipitate with calcium ions in joints and other soft tissues. The main concern regarding hyperphosphatemia is the underlying condition that caused the increased concentration. For instance, ingestion of large amounts of phosphosoda can result in acute hyperphosphatemia but also acute renal failure and, often, chronic kidney disease (CKD)  . The prognosis of a short term elevation in phosphate is good; however, in chronic hyperphosphatemia the prognosis is often mixed. Excess of phosphate for a long period of time can damage most organ systems. The cardiovascular system, bones, joints, and skin are most susceptible to damage by chronic hyperphosphatemia. In CKD, prolonged hyperphosphatemia is an independent risk factor for cardiovascular disease. This population has an 18-39% higher mortality rate if their phosphate levels exceed 6.5 mg/dL compared to patients with CKD and normal or even slightly elevated phosphate levels.
Renal disease and Hyperphosphatemia
Mortality rates are higher in patients with hyperphosphatemia and kidney transplant, chronic kidney disease and end-stage renal disease . Preventing this condition early in the course of kidney failure can prevent or postpone the development of chronic hyperphosphatemia complications. In this population the key is to prevent ingestion and absorption with dietary changes and using oral phosphate binders that neutralize phosphate in the gastrointestinal system, allowing it to pass with the stool instead of being absorbed by the small intestine. If elevated phosphate levels are not addressed, then pathologic changes will occur in joints, bones, vascular tissue and other soft tissues. These changes are usually permanent.
Phosphate levels in the blood rise when any of the following conditions are present :
Phosphate and phosphorous are absorbed through the upper half of the small intestine. Any excess phosphate absorbed by the gastrointestinal system is excreted by the kidneys under normal circumstances. If the kidneys are injured or hypoperfused, then even a minor dietary phosphate increase may lead to hyperphosphatemia. Phosphate absorption in the gut and excretion by the kidneys is regulated by vitamin D. Excess vitamin D can also lead to hyperphosphatemia by increasing absorption rates.
Hyperphosphatemia may result from excessive phosphate intake via any of these mechanisms:
- Phosphorus poisoning
- Liberal use of saline phosphate enemas
- Excess vitamin D intake 
- Phosphate injections (IV or IM)
- Milk-alkali syndrome
Kidney injury may result in a reduction of phosphate excretion. Patients with poor kidney function have to carefully regulate their dietary phosphate levels. Vitamin D regulates phosphate absorption in the gastrointestinal system and reabsorption in healthy kidneys. Increased levels of Vitamin D result in the reabsorption of more phosphate by the tubules of the kidneys and less excretion. Reabsorbed phosphate re-enters the blood and increases plasma concentration. This process is balanced by parathyroid hormone (PTH), which is secreted by the parathyroid gland. PTH stimulates the kidneys to excrete phosphate. When PTH levels are low, more phosphate is reabsorbed by the kidneys. Therefore, hypoparathyroidism can lead to hyperphosphatemia.
Hyperphosphatemia may result from reduced phosphate excretion via any of these mechanisms:
- Excessive vitamin D
- Acute and chronic kidney injury
- Kidney failure
- Magnesium deficiency
- Multiple myeloma
Phosphate shift from the intracellular space to the extracellular space
A majority of the phosphate in the body is stored in the bones. A much smaller portion is used by cells and an even smaller portion is found circulating in the blood. Under certain circumstances the intracellular phosphate is released into the blood. This can contribute to hyperphosphatemia. Circumstances under which phosphate can be released into the circulation include:
Hyperphosphatemia is a rare condition. It is more common in patients with advanced chronic kidney disease and acute kidney disease. In this population the prevalence approaches 70%. Dialysis-dependent kidney failure also poses a major risk for developing hyperphosphatemia. These trends are similar in the developed and developing worlds.
Phosphate ion concentration is not measured directly in the blood. However, calcium is carefully measured. Vitamin D and parathyroid hormone are secreted in response to calcium levels. Plasma phosphorous levels change as calcium levels are adjusted. Bones and cells absorb and release calcium and phosphate in response to these signals. The gastrointestinal system and kidneys absorb and excrete phosphate and calcium in response to these hormone signals as well. Hyperphosphatemia is the result of an excessive phosphate load and three mechanisms can induce this imbalance :
- Increased phosphate intake by the GI system.
- Decreased phosphate excretion by the kidneys.
- Intracellular shift of phosphate ions to the extracellular space.
The signs and symptoms of hyperphosphatemia are the same irrespective of the cause. A healthy patient can ingest large quantities of phosphate without developing hyperphosphatemia due to tissue absorption and kidney excretion.
Reducing and eliminating phosphate and phosphorous from the diet is necessary and effective in any treatment protocol. This step alone may normalize phosphate levels in the blood, but it is unlikely to treat the underlying condition. Phosphorous is found in many foods. These include the following:
Dark green vegetables and grain:
Hyperphosphatemia is a result of an imbalance in the absorption and excretion of phosphate. When phosphorus is oxidized it transforms into phosphate ions (PO43-), the most common form of phosphorous in the body. Both the ion and elemental forms are absorbed by the gastrointestinal system and are excreted by the kidneys. It is also excreted through the loss of gastrointestinal cells that are replaced at a rapid pace. Vitamin D and other hormones regulate the absorption, storage, and excretion of phosphate . Phosphate ions are biologically important. Only a very small number of phosphate ions are found in the blood, yet they have many roles throughout the body. They are an integral part of the mineral matrix that forms the skeleton . The bones store a majority of the body’s total phosphate concentration and this phosphate is in constant flux with calcium and magnesium. In cells, phosphate forms adenosine triphosphate (ATP), a major source for chemical energy in the cell and a coenzyme that regulates many intracellular enzymes. Phosphate is also a significant part of DNA and RNA, and a component of cell membranes.
Hyperphosphatemia describes the condition of elevated phosphate ions in the blood. Hyperphosphatemia may be described as high levels of phosphate ions in the blood. Normal range for phosphorous is 2.5-4.5 mg/dL; however, normal values vary slightly from laboratory to laboratory. Phosphate is used with calcium to form bones, and it is found in all types of cells in the body. Just as vitamin D is an important regulator of calcium in the body, it also regulates the absorption and excretion of phosphate.
Elevated phosphate levels in the blood (hyperphosphatemia) is often caused by the kidney's inability to excrete sufficient amounts to maintain balance. This condition is seen with:
- Acute and chronic kidney injury.
- Elevated levels of vitamin D.
- Increased intake, seen with excess use of enemas or laxatives that contain phosphate.
- Cell breakdown, seen in chemotherapy (tumor lysis syndrome open link) or rhabdomyolysis (skeletal muscle destruction associated with crush injuries and excess exercise).
- Slow breathing for long periods of time (respiratory acidosis).
- Parathyroid abnormalities.
Sign and symptoms
Patients with hyperphosphatemia are usually symptom-free. There is usually an underlying condition (for example, kidney failure) causing this electrolyte disorder and there may be symptoms associated with that underlying condition.
A blood test is used to diagnose hyperphosphatemia. Usually a plethora of tests are performed to assist in diagnosing the underlying condition.
Treating elevated levels of phosphate in the blood and the underlying condition should be accomplished in tandem. The most effective way to reduce phosphate levels is to limit phosphate intake and absorption through the intestinal lining. Phosphate binders are oral medications that bind to and neutralize phosphorous and phosphate in the gut, allowing it to pass without absorption into the blood. Other medication includes diuretics that help to excrete phosphate with the urine. Dialysis is effective in cases of chronic kidney disease.
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