eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hypophosphatemia: Treatment & Medication

Author: Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Coauthor(s): Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Aug 7, 2009

Treatment

Medical Care

Medical care is highly dependent on 3 factors: cause, severity, and duration. Phosphate distribution varies among patients, so no formulas reliably determine the magnitude of the phosphate deficit. The average patient requires 1000-2000 mg (32-64 mmol) of phosphate per day for 7-10 days to replenish the body stores.

  • When a treatable cause of the hypophosphatemia is known, then treatment of that underlying cause is of paramount importance and is often curative.
    • For example, refeeding hypophosphatemia can be anticipated in patients who have a strong history of alcoholism, starvation, or anorexia/bulimia. Adequate treatment includes phosphate supplements in addition to feeding and attention to underlying eating disorders or substance abuse.
    • A likely successful therapy for treating malabsorption due to celiac disease or Crohn disease is specific therapy directed at the underlying illness, with the addition of vitamin D supplements.
  • Oral phosphate supplements, although not curative, are useful for the treatment of the genetic disorders of phosphate wasting and can often normalize phosphate levels and decrease bone pain.
    • The patient's serum phosphate level, calcium level, bone density, and growth should be monitored frequently to ensure adequacy of treatment.
    • Oral phosphate supplements are also useful for the treatment of possible oncogenic osteomalacia until the time when the tumor can be identified and surgically removed. Oral phosphate supplements are well tolerated except in high doses, which can produce diarrhea.
    • For very mild hypophosphatemia, increased oral phosphate intake from diet alone may be adequate. Foods that are high in phosphate include dairy items, meats, and beans.
  • Parenteral phosphate supplementation is generally reserved for patients who have life-threatening hypophosphatemia or nonfunctional gastrointestinal syndromes.
    • In contrast to oral phosphate supplements, parenteral phosphate administration is more likely to have complications. Administration that is too rapid can result in hypocalcemia, tetany, and hypotension.
    • Other complications that may occur include metastatic calcification, hyperkalemia associated with potassium-containing supplements, volume excess, hypernatremia, metabolic acidosis, and hyperphosphatemia.
    • Suggested rates of safe delivery of phosphate range from 1-3 mmol/h. Each milliliter of sodium or potassium phosphate solution has 3 mmol/mL; therefore, this translates to 0.3-1 mL/h. An easy to use weight-based regimen involves administering 0.08 mmol/kg (2.5 mg/kg) or 0.16 mmol/kg (5 mg/kg) over 6 hours, depending on the severity of the expected phosphate deficit.
    • More rapid correction has been found to be safe, but the magnitude of the response can be unpredictable. Serum phosphate and calcium levels should be monitored every 6 hours to ensure maintenance of normal calcium levels and to prevent overcorrection of phosphate deficiency.
  • The management of patients with hypophosphatemia can be divided into various subgroups based on the severity of the hypophosphatemia and the need for ventilation.
    • Severe hypophosphatemia (<1.0 mg/dL [0.3 mmol/L]) in critically ill, intubated patients or in those with clinical sequelae of hypophosphatemia (eg, hemolysis) should be managed with intravenous replacement therapy (0.08–0.16 mmol/kg) over 2-6 hours.
    • Moderate hypophosphatemia (1.0–2.5 mg/dL [0.3–0.8 mmol/L]) in patients on a ventilator should be managed with intravenous replacement therapy (0.08–0.16 mmol/kg) over 2-6 hours.
    • Moderate hypophosphatemia (1.0–2.5 mg/dL [0.3–0.8 mmol/L]) in nonventilated patients should be managed with oral replacement therapy (1000 mg/d).
    • Mild hypophosphatemia should be managed with oral replacement therapy (1000 mg/d).
  • Vitamin D supplementation is appropriate for patients with vitamin D deficiency.
    • Most patients respond to oral vitamin D-2 supplements, commonly available in over-the-counter multivitamin preparations.
    • Because the kidneys are responsible for the final 1-alpha hydroxylation of vitamin D, patients with significant renal insufficiency may not be able to metabolize liver-derived 24 hydroxyvitamin D-3 to its active dihydroxy form. These patients benefit from oral 1,25 dihydroxyvitamin D-3 supplements. Because vitamin D enhances calcium and phosphate absorption, frequent monitoring of both is required.

Surgical Care

Patients with primary hyperparathyroidism benefit from parathyroidectomy. For patients in whom parathyroidectomy is not feasible, treatment with the new calcium mimetic agents has shown demonstrable control of hyperparathyroidism. Patients with oncogenic osteomalacia are cured by excision of the tumor causing the phosphate wasting and relative vitamin D deficiency.

Consultations

  • An endocrinologist might be helpful if the diagnosis of primary hyperparathyroidism is not readily apparent, especially to exclude the possibility of familial hypocalciuric hypercalcemia. In conjunction with a surgeon, an endocrinologist can help assess the patient for the different potential therapies for primary hyperparathyroidism and choose the best individual therapy.
  • A gastroenterologist may help in establishing a diagnosis of malabsorption and in pinpointing the cause. Input from this consultant can also be very useful in formulating the most effective therapy and patient education.
  • A nephrologist can help confirm the likelihood of phosphate wasting and can help assess the patient for causes of renal phosphate wasting.
  • A surgeon is required for parathyroidectomy or for removal of a tumor causing oncogenic osteomalacia.
  • A psychiatrist should be requested for patients with a self-imposed eating disorder such as anorexia or bulimia. These common disorders can be fatal and are often difficult to treat. Psychiatric intervention often requires years to effect a remission.

Diet

A regular diet generally provides all of the phosphate required for the day and more. For patients with phosphate wasting, high-phosphate diets (including dairy products, meats, and beans) should be encouraged, along with phosphate supplements. Cow’s milk, an excellent and accessible source of phosphate, contains 1 mg (0.032 mmol) of elemental phosphate per milliliter. Consumption of vitamin D–supplemented foods should also be encouraged.

Activity

For transient mild hypophosphatemia, no activity restrictions are necessary. For chronic phosphate wasting syndromes, the degree of bone disease is the best guide for assessing activity. Severe osteomalacia puts patients at high risk for fracture. Notably, these patients often have accompanying proximal muscle weakness and muscle pain that in and of themselves restrict activity. These patients with established osteomalacia should avoid high-impact activities and should practice fall precautions.

Medication

The goals of pharmacotherapy are to increase serum phosphate levels, to reduce morbidity, and to prevent complications.

Mineral supplements

Phosphate salts are used to increase serum phosphate levels.


Phosphate salts (Neutra-Phos-K)

For severe hypophosphatemia ( <1 mg/dL), use parenteral preparations of phosphate for repletion. IV preparations are available as sodium or potassium phosphate. Response to IV serum phosphorus supplementation is highly variable and can be associated with hyperphosphatemia and hypocalcemia. Infusion rate and choice of initial dosage is based on severity of hypophosphatemia and presence of symptoms. Closely monitor serum phosphate and calcium levels.
For less severe hypophosphatemia (1-2 mg/dL), PO phosphate salt preparations can be used. PO preparations are available as sodium or potassium phosphate in cap or liquid form. Neutra-Phos packets contain 250 mg of phosphorus/packet. Tabs contain 250, 125.6, or 114 mg apiece. Liquid preparations are available as 250 mg/75 mL.

Adult

Initial dose: 0.1 mmol/kg of q6h IV (32 mmol/d)
Aggressive IV replacement: 0.2-0.3 mmol/kg over 6 h
PO replacement: 250 mg as cap, liquid, or packet tid/qid generally adequate; for most patients, once phosphate stores are repleted, PO supplements are no longer required because most diets have ample phosphate

Pediatric

0.25-0.5 mmol/kg PO over 4-6 h; repeat if symptomatic hypophosphatemia persists

Magnesium- and aluminum-containing antacids or sucralfate can act as phosphate binders and decrease serum phosphate levels; potassium-sparing diuretics, ACE inhibitors, and salt substitutes may increase serum phosphate levels

Documented hypersensitivity; patients diagnosed with hyperphosphatemia, hypocalcemia, hypomagnesemia, hyperkalemia, or renal failure

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with renal insufficiency and metabolic alkalosis; admixture of phosphate and calcium in IV fluids can result in calcium phosphate precipitation; with use of IV preparations, monitor carefully for hypotension, hypocalcemia, tetany, or hypophosphatemia; with PO preparations, monitor for development of diarrhea

Vitamin D preparations

Vitamin D enhances intestinal and renal absorption of phosphate. Can be administered in addition to phosphate supplements to increase serum phosphate and total body phosphate stores.


Ergocalciferol (vitamin D-2)

Requires conversion to active 1,25 dihydroxy cholecalciferol in kidneys. Administered PO.

Adult

10,000-80,000 U/d PO

Pediatric

Administer as in adults

Cholestyramine, mineral oil, and colestipol decrease absorption

Documented hypersensitivity; hypercalcemia, hyperphosphatemia

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Monitor serum calcium and phosphorus carefully, especially in patients with some degree of renal insufficiency; levels of both can increase dramatically and suddenly; can also promote hypercalciuria, potentiating the possibility of kidney stones; patients with advanced renal insufficiency do not respond well because of the need for conversion to the active form in the kidneys


Calcitriol (Calcijex, Rocaltrol)

Active form of vitamin D, 1,25 dihydroxyvitamin D-3. Use in patients with renal failure who are unable to convert inactive prohormone forms to active metabolite. Available in PO and parenteral form.

Adult

0.25 mcg/d PO initially; increase to 1 mcg/d as determined by levels of serum phosphorus and as tolerated by monitoring serum calcium level
Alternatively, administer 0.1-0.2 mcg/d IV

Pediatric

Initial: 15 ng/kg/d PO
Maintenance: 5-40 ng/kg/d PO

Cholestyramine and colestipol decrease absorption; magnesium-containing antacids and thiazide diuretics can increase effects

Documented hypersensitivity; hypercalcemia, malabsorption syndrome

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adequate response depends on adequate dietary calcium intake; maintain adequate fluid intake; monitor for hypercalcemia and hyperphosphatemia, especially in patients with renal insufficiency


Doxercalciferol (Hectorol)

Requires hydroxylation in liver to be converted to an active vitamin D metabolite. May cause less toxicity than calcitriol with regard to calcium homeostasis. Predominantly used to treat secondary hyperparathyroidism of renal failure

Adult

10 mcg PO at dialysis; then adjust dose per endpoints desired

Pediatric

Not established

Cholestyramine and mineral oil may reduce absorption; patients with hypoparathyroidism taking vitamin D may develop hypercalcemia due to thiazide diuretics; concurrent use with other vitamin D supplements or magnesium-containing antacids (or supplements) may increase toxicity

Documented hypersensitivity; hyperphosphatemia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Discontinue other forms of vitamin D before initiating therapy; avoid overdose; monitor calcium levels carefully; hyperphosphatemia may reduce effects; caution in hepatic impairment


Paricalcitol (Zemplar)

Vitamin D-3 analogue available in parenteral form and predominantly used to treat secondary hyperparathyroidism of renal failure, especially when calcitriol treatment has resulted in hypercalcemia. Appears to have a lesser effect on calcium and phosphorus metabolism than calcitriol. For this reason, it is not as useful as calcitriol for the treatment of hypophosphatemia.

Adult

0.04 mcg/kg IV bolus after dialysis; then adjust dose per endpoints desired

Pediatric

Not established

Patients with hypoparathyroidism taking vitamin D may develop hypercalcemia due to thiazide diuretics; concurrent use with other vitamin D supplements or magnesium-containing antacids (or supplements) may increase toxicity

Documented hypersensitivity; hypercalcemia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Calcium and phosphorus level should be monitored carefully, especially in patients with renal failure; once dosage has been established, measure serum calcium and phosphate levels at least monthly; measurements of serum or plasma PTH levels are recommended every 3 mo

Calcimimetic drugs

This category of drug activates the calcium sensing receptor on parathyroid gland cells, thus diminishing the release of parathyroid hormone. These agents are useful for the control of hyperparathyroidism in patients who are unwilling to undergo surgery or who are suboptimal candidates for surgery.


Cinacalcet (Sensipar)

This drug is available in oral form and has to be taken daily for desired effect. To monitor efficacy, the drug should be taken at the same time every day and the intact parathyroid hormone (iPTH) level should also be taken at the same time every time it is checked. The clinician needs to monitor also for the development of hypocalcemia.

Adult

30 mg PO qd initially; titrate upward slowly (no more frequent than q2-4wk intervals) by 30 mg increments to target iPTH of 150-300 pg/mL
Take with meals or immediately following; do not crush, chew or cut tablets

Pediatric

Not established

Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting

More on Hypophosphatemia

Overview: Hypophosphatemia
Differential Diagnoses & Workup: Hypophosphatemia
Treatment & Medication: Hypophosphatemia
Follow-up: Hypophosphatemia
References
Further Reading
[ CLOSE WINDOW ]

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Keywords

hypophosphatemia, rickets, osteomalacia, vitamin D deficiency, deficiency of vitamin D, phosphate level, phosphate levels, serum phosphate, low phosphate, hereditary hypophosphatemic rickets, Fanconi syndrome, Fanconi's syndrome, celiac sprue, renal tubular reabsorption, phosphate homeostasis, parathyroid hormone, PTH, renal phosphate excretion, rhabdomyolysis, phosphate-wasting syndrome, phosphate wasting syndrome, parathyroidectomy, hyperparathyroidism

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Contributor Information and Disclosures

Author

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Rosemary Ouseph, MD, Professor of Medicine, Director of Kidney Transplant, University of Louisville School of Medicine
Rosemary Ouseph, MD is a member of the following medical societies: American Society for Bone and Mineral Research, American Society of Nephrology, and American Society of Transplant Surgeons
Disclosure: Nothing to disclose.

Medical Editor

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians
Disclosure: Genzyme Grant/research funds Other

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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