Hypophosphatemia: Evaluation and treatment

INTRODUCTION — Hypophosphatemia is defined as a serum phosphorus concentration that is below the age-appropriate normal range (eg, less than 2.5 mg/dL [0.81 mmol/L] in adults). Hypophosphatemia can be induced by decreased net intestinal absorption, increased urinary phosphate excretion, or acute movement of extracellular phosphate into cells.

This topic will review the evaluation and treatment of patients with hypophosphatemia. The causes of hypophosphatemia and clinical manifestations of phosphate depletion are discussed separately:

●(See "Hypophosphatemia: Causes of hypophosphatemia".)

●(See "Hypophosphatemia: Clinical manifestations of phosphate depletion".)

EVALUATION — The evaluation of hypophosphatemia begins by excluding spurious hypophosphatemia (pseudohypophosphatemia). Patients with true hypophosphatemia should be evaluated by history and laboratory testing to identify the underlying cause. If the cause is not apparent, measurement of urinary phosphate excretion can be helpful to distinguish between gastrointestinal and renal phosphate losses.

Exclude pseudohypophosphatemia — Spurious hypophosphatemia (pseudohypophosphatemia) may occur in certain clinical settings and should be excluded to avoid unnecessary testing and treatment of hypophosphatemia. It is usually caused by paraproteins (eg, in patients with multiple myeloma or other monoclonal gammopathies) or medications (eg, liposomal amphotericin, large doses of intravenous [IV] mannitol) that interfere with the phosphate assay [1].

If pseudohypophosphatemia due to paraprotein interference is suspected, dilution of the blood sample with normal saline or using a protein-free filtrate prepared with trichloroacetic acid can help to eliminate the artifact [2,3].

History and initial laboratory testing — Patients with true hypophosphatemia should be evaluated to identify the underlying cause, which is usually apparent from the history (table 1). (See "Hypophosphatemia: Causes of hypophosphatemia".)

In patients with unexplained hypophosphatemia, we perform the following initial evaluation:

●We repeat the serum phosphorus concentration to determine if the hypophosphatemia is persistent. Transient hypophosphatemia (eg, due to redistribution of phosphate) usually resolves within 6 to 12 hours as long as the underlying cause is corrected. No further evaluation of hypophosphatemia is required if the hypophosphatemia has resolved and there are no worrisome clinical findings. (See "Hypophosphatemia: Clinical manifestations of phosphate depletion".)

●We review the patient's medications to assess for drugs that can potentially cause hypophosphatemia (table 2). (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Medications' and "Hypophosphatemia: Causes of hypophosphatemia", section on 'Miscellaneous'.)

●We review the patient's dietary history to assess for malnutrition. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Inadequate intake'.)

●We review serum biochemical parameters, including bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, and magnesium levels. Reviewing the serum calcium level can identify the two most common causes of hypophosphatemia:

•If calcium is high, we measure parathyroid hormone (PTH) to assess for hyperparathyroidism. Even in severe hyperparathyroidism, serum phosphorus is almost never below 1.5 to 2 mg/dL. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation".)

•If calcium is low, we measure 25-hydroxyvitamin D to assess for vitamin D deficiency. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Vitamin D insufficiency and deficiency in children and adolescents".)

Assessment of urinary phosphate excretion — If the cause of hypophosphatemia is still not apparent from the history and initial laboratory testing, measurement of urinary phosphate excretion can be helpful to distinguish between gastrointestinal and renal phosphate losses. The normal kidney response to phosphate depletion is to increase phosphate reabsorption, leading to the virtual abolition of phosphate excretion in the urine.

Phosphate excretion can be measured either from a 24-hour urine collection or by calculation of the fractional excretion of filtered phosphate (FEPO4) from a random urine specimen.

The formula used to calculate the FEPO4 (calculator 1) is similar to that used to calculate the fractional excretion of sodium (FENa):

where U and P refer to the urine and plasma concentrations of phosphate (PO4) and creatinine (Cr).

In patients with hypophosphatemia:

●A 24-hour urine phosphate excretion less than 100 mg or a FEPO4 less than 5 percent indicates appropriately low renal phosphate excretion, suggesting that the hypophosphatemia is caused by internal redistribution (eg, refeeding syndrome, acute respiratory alkalosis) or decreased intestinal absorption (eg, chronic antacid therapy, steatorrhea). (See 'Low phosphate excretion' below.)

●A 24-hour urine phosphate excretion greater than or equal to 100 mg or a FEPO4 greater than or equal to 5 percent indicates renal phosphate wasting, suggesting that the hypophosphatemia is caused by excess production of phosphaturic hormones (eg, hyperparathyroidism, increased circulating concentrations of fibroblast growth factor 23 [FGF23]) or a variety of other conditions. (See 'Inappropriately high phosphate excretion' below.)

Urinary phosphate measurements are most reliable for assessing inappropriate urinary phosphate excretion in the absence of active phosphate repletion. Thus, it is best for the measurement to be performed prior to initiating supplementation. If phosphate supplementation has been initiated, we typically pause supplementation for at least 24 hours prior to urine collection for phosphate quantification and measure serum phosphorus at the time of the urine collection.

Low phosphate excretion — The normal kidney response to hypophosphatemia is to reduce daily phosphate excretion below 100 mg and the FEPO4 to well below 5 percent (the normal FEPO4 is 5 to 20 percent). If the kidney response is normal, then renal phosphate wasting is not the cause of the hypophosphatemia. A review of the basic aspects of renal phosphate handling is presented separately. (See "Hypophosphatemia: Causes of hypophosphatemia".)

Hypophosphatemia in patients with an appropriately low urinary FEPO4 (or 24-hour urinary phosphate excretion) is usually caused by either increased cellular uptake (internal redistribution) and/or reduced intestinal phosphate absorption (table 1):

●Increased cell entry may be generated by glucose and/or insulin infusions (as in a refeeding state or during the treatment of uncontrolled diabetes mellitus) or as a result of acute respiratory alkalosis (as in patients with hyperventilation). (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Internal redistribution'.)

●In the absence of these conditions, the most likely cause of the hypophosphatemia is decreased intestinal absorption of phosphate. Mechanisms that promote high fecal excretion of phosphate include:

•Rapid intestinal transit and increased secretions (as seen with chronic diarrhea).

•Intestinal phosphate binding within the intestinal lumen by ingestion of soluble calcium, magnesium, and/or aluminum salts, which then form insoluble phosphate salts (as observed with chronic antacid therapy).

•Inhibition of intestinal phosphate transport (as occurs with niacin therapy) [4,5]. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Decreased intestinal absorption'.)

Inappropriately high phosphate excretion — Urinary phosphate excretion above 100 mg/day or a FEPO4 above 5 percent is indicative of renal phosphate wasting in patients with hypophosphatemia. This is usually due to hyperparathyroidism, increased activity of phosphatonins such as FGF23, or generalized proximal tubule dysfunction. All of these conditions reduce renal tubule phosphate absorption by diminishing the activity of the sodium-phosphate cotransporters (NaPi-IIa and NaPi-IIc) in the proximal tubule (table 1) [6]. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Increased urinary excretion'.)

To distinguish between these different causes of renal phosphate wasting, we suggest the following diagnostic approach:

●Assess for generalized proximal tubule dysfunction (Fanconi syndrome) – Proximal tubule dysfunction is suggested by the presence of other abnormalities in proximal reabsorption, including glucosuria (at a normal plasma glucose concentration), hypouricemia, aminoaciduria, and a hyperchloremic metabolic acidosis due to urinary bicarbonate wasting. Thus, we assess the patient for generalized proximal tubule dysfunction by measuring urinary levels of glucose, protein, and amino acids, as well as serum levels of bicarbonate and uric acid. The major causes of the Fanconi syndrome are cystinosis, Wilson disease, multiple myeloma (in which filtered light chains are toxic to the proximal tubule), heavy metal toxicity, and medications (particularly nucleotide analog reverse transcriptase inhibitors [such as tenofovir] and ifosfamide). (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Fanconi syndrome' and "Etiology and diagnosis of distal (type 1) and proximal (type 2) renal tubular acidosis", section on 'Proximal (type 2) RTA'.)

●Differentiate between hyperparathyroidism and phosphatonin-mediated hypophosphatemia – If the patient has isolated urinary phosphate wasting without generalized proximal tubule dysfunction, we obtain the following tests (if not already available):

•Serum calcium

•Serum PTH

•Serum FGF23 (if available)

•Serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D

In general, isolated urinary phosphate wasting is due to either excess PTH (hyperparathyroidism) or excess FGF23 (phosphatonin-mediated hypophosphatemia):

•Hyperparathyroidism – Hypophosphatemia can be seen with either primary or secondary hyperparathyroidism. The triad of hypercalcemia, hypophosphatemia, and urinary phosphate wasting is often present in primary hyperparathyroidism. By contrast, hypocalcemia is a major stimulus for hypersecretion of PTH in secondary disease. Hypophosphatemia and urinary phosphate wasting in a patient without hypercalcemia should prompt an evaluation for vitamin D deficiency. The evaluation and diagnosis of hyperparathyroidism is discussed in detail separately. (See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation".)

•Phosphatonin-mediated hypophosphatemia – Increased circulating concentrations of FGF23 (or other less characterized phosphatonins) can result in isolated phosphaturia with no other obvious defects in kidney tubular function. In patients with FGF23-mediated hypophosphatemia, the serum concentrations of PTH and 25-hydroxyvitamin D are usually normal. However, the 1,25-dihydroxyvitamin D level is low or inappropriately normal due to suppression of 1-alpha-hydroxylase activity by FGF23.

FGF23-mediated hypophosphatemia can be observed in a variety of clinical settings, including patients receiving ferric carboxymaltose therapy for treatment of iron deficiency anemia [7,8], children with certain genetic mutations leading to vitamin D–resistant rickets, or adults with tumor-induced osteomalacia (TIO), a condition characterized by the overproduction of phosphaturic substances produced by mesenchymal tumors (usually a hemangiopericytoma). A major consequence of persistently elevated serum FGF23 and the resulting phosphaturia is defective bone mineralization (osteomalacia), which portends substantial long-term risk of fractures. A more extensive discussion of the clinical features and diagnosis of phosphate wasting syndromes is provided separately. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Primary renal phosphate wasting' and "Hypophosphatemia: Causes of hypophosphatemia", section on 'Miscellaneous' and "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia".)

TREATMENT — Treatment of the underlying cause of hypophosphatemia is usually sufficient to resolve the hypophosphatemia in many cases. Some patients will require phosphate supplementation depending upon the serum phosphorus concentration and the presence of symptoms of hypophosphatemia.

Treatment of the underlying cause — Patients with hypophosphatemia should be treated for the underlying cause. In many cases, treatment of the underlying cause will be sufficient to resolve the hypophosphatemia without the need for phosphate repletion. As examples:

●Hypophosphatemia occurring during the correction of diabetic ketoacidosis will correct spontaneously with normal dietary intake. Trials of routine phosphate supplementation have not shown benefit, but such therapy may be warranted in patients with severe symptomatic hypophosphatemia. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Serum phosphate' and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment", section on 'Phosphate depletion'.)

●Patients who have hypophosphatemia due to gastrointestinal losses should correct spontaneously once there is resolution of the underlying cause (eg, diarrhea, chronic antacid therapy, or vitamin D deficiency). Specific recommendations for vitamin D supplementation are presented elsewhere. (See "Hypophosphatemia: Causes of hypophosphatemia" and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

●Patients who undergo surgical treatment of primary hyperparathyroidism should have resolution of their hypophosphatemia unless they develop hungry bone syndrome after parathyroidectomy. (See "Primary hyperparathyroidism: Management" and "Hypophosphatemia: Causes of hypophosphatemia", section on 'Hungry bone syndrome'.)

Phosphate repletion — In addition to treatment of the underlying cause of hypophosphatemia, some patients will require phosphate supplementation.

Approach to repletion — Our approach to phosphate repletion takes into account the serum phosphorus concentration, the presence of overt symptoms of hypophosphatemia, and whether the patient can take oral therapy. In general, patients with a serum phosphorus concentration below 2 mg/dL (0.64 mmol/L) should receive phosphate supplementation.

If possible, we prefer oral rather than intravenous (IV) phosphate therapy since IV repletion can lead to transient hyperphosphatemia that may result in serious complications such as hypocalcemia, acute kidney injury, and arrhythmias. However, in patients who are unable to take or tolerate oral phosphate supplementation and in patients with extremely low serum phosphorus levels, especially those with symptomatic hypophosphatemia, IV repletion is reasonable.

We suggest the following approach (algorithm 1):

●If the serum phosphorus is <1 mg/dL (0.32 mmol/L), we treat with IV phosphate. We switch to oral phosphate when the serum phosphorus exceeds 1.5 mg/dL (0.48 mmol/L).

●If the serum phosphorus is 1 to 2 mg/dL (0.32 to 0.64 mmol/L), treatment varies with the presence or absence of overt symptoms of hypophosphatemia and the severity of hypophosphatemia:

•In asymptomatic patients, we give oral phosphate therapy. Many of these patients may have myopathy and weakness that are not clinically apparent.

•In symptomatic patients whose serum phosphorus is 1 to 1.5 mg/dL (0.32 to 0.48 mmol/L), we treat with IV phosphate and switch to oral phosphate when the serum phosphorus exceeds 1.5 mg/dL (0.48 mmol/L).

•In symptomatic patients whose serum phosphorus is >1.5 to 2 mg/dL (0.48 to 0.64 mmol/L), we treat with oral phosphate therapy.

●We stop phosphate repletion when the serum phosphate is ≥2 mg/dL (0.64 mmol/L) unless there is an indication for chronic therapy such as persistent urinary phosphate wasting.

Oral repletion is most often achieved with a combined preparation of sodium and potassium phosphate; sodium phosphate is preferred for IV therapy. (See 'Oral dosing' below and 'Intravenous dosing' below.)

Phosphate repletion regimens

Oral dosing — When oral dosing is used, we initiate therapy with 30 to 80 mmol of phosphate per day in divided doses (table 3). Phosphate may also be supplemented with skim milk, which contains approximately 8 mmol of phosphate per 237 mL serving (1 cup).

The following regimen is a reasonable approach:

●If the serum phosphorus is >1.5 to 2 mg/dL (0.48 to 0.64 mmol/L), we give 1 mmol/kg of elemental phosphorus (minimum of 40 mmol and a maximum of 80 mmol) in three to four divided doses over 24 hours.

●If the serum phosphorus is 1 to 1.5 mg/dL (0.32 to 0.48 mmol/L), we give 1.3 to 1.4 mmol/kg of elemental phosphorus (up to a maximum of 100 mmol) in three to four divided doses over 24 hours.

●Patients with severe obesity may receive the maximal initial doses or an adjusted dose based upon their height and weight (calculator 2).

●Patients with a reduced glomerular filtration rate should receive approximately one-half of the suggested initial dose.

The serum phosphorus concentration should be rechecked 2 to 12 hours following the last of the divided doses to determine whether repeated doses are required. If so, the same approach may be reapplied.

Oral phosphate supplements (tablets and powders) contain varying ratios of sodium and potassium phosphate (table 3). Serious medication errors have occurred due to confusion among preparations and lack of uniformity of units on product labels and when ordering. Thus, an oral phosphate supplement should be selected with consideration of its potassium and sodium content and dosed according to mmol of phosphate. Commonly used oral potassium phosphate-sodium phosphate supplements include 250 mg (8 mmol) of phosphate per tablet.

Intravenous dosing — IV phosphate is potentially dangerous since it can precipitate with calcium and produce a variety of adverse effects including hypocalcemia due to binding of calcium, kidney failure due to calcium phosphate precipitation in the kidneys, and possibly fatal arrhythmias.

If IV therapy is necessary in patients with severe symptomatic hypophosphatemia or an inability to take oral therapy, we suggest a dose that varies depending upon the severity of the hypophosphatemia and the weight of the patient. We suggest the following regimen [9,10]:

●If the serum phosphorus concentration is ≥1.4 mg/dL (0.45 mmol/L), we give 0.2 mmol/kg over four hours (up to a maximum dose of 20 mmol for initial dosing).

●If the serum phosphorus concentration is ≥1.1 to 1.3 mg/dL (0.36 to 0.42 mmol/L), we give 0.3 mmol/kg over four hours (up to a maximum dose of 30 mmol for initial dosing)

●If the serum phosphorus is ≤1 mg/dL (0.32 mmol/L), we give 0.4 mmol/kg over six hours (up to a maximum dose of 50 mmol for initial dosing).

The serum phosphate concentration should be monitored every six hours when IV phosphate is given, and the patient should be switched to oral replacement when the serum phosphate concentration reaches 1.5 mg/dL (0.48 mmol/L) [11].

IV phosphate is available as potassium phosphate or sodium phosphate (table 3); serum potassium levels may guide product selection. Potassium phosphate provides approximately 1.5 mEq of potassium for each 1 mmol of phosphate. To prevent medication errors, the dose should be expressed as mmol of phosphate, and sodium or potassium salt should be specified.

Risks of long-term phosphate therapy — The primary concern with chronic phosphate therapy is an increased risk for extraskeletal mineral deposition, particularly in the kidney. In patients with chronic phosphaturia, long-term administration of phosphate supplements can increase the risk for nephrocalcinosis and presumably contribute to a gradual loss of kidney function [12,13]. Individuals receiving chronic phosphate supplementation should undergo periodic measurement of serum phosphorus and creatinine to monitor phosphate balance and kidney function, as well as intermittent kidney ultrasound to assess for the development of nephrocalcinosis.

Special considerations — Several patient populations that commonly develop hypophosphatemia require unique attention when treating this disorder.

Patients with alcohol use disorder — Patients with alcohol use disorder are prone to severe hypophosphatemia, particularly when admitted to the hospital. However, the fall in serum phosphorus, occasionally to less than 1 mg/dL (0.32 mmol/L), may not become prominent until 12 to 36 hours after admission, due to movement of extracellular phosphate into cells [14]. Thus, serial monitoring of the serum phosphorus concentration is warranted when patients with alcohol use disorder are admitted to the hospital. (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Internal redistribution'.)

●Phosphate repletion – The general approach to phosphate repletion in patients with alcohol use disorder is similar to that for patients without alcohol use disorder and is discussed above. (See 'Approach to repletion' above.)

●Avoidance of dextrose-containing fluids – As mentioned above, hypophosphatemia in patients with alcohol use disorder often occurs or is exacerbated after admission to the hospital due to phosphate movement from the extracellular fluid into cells. This may be driven in part by the release of insulin following the administration of dextrose-containing IV fluids. Thus, dextrose-containing fluids should not be given in patients who are hypophosphatemic at presentation and who do not have an indication for dextrose therapy (eg, hypoglycemia, alcoholic ketoacidosis). (See "Fasting ketosis and alcoholic ketoacidosis".)

●Vitamin D – Vitamin D deficiency may contribute to hypophosphatemia in patients with alcohol use disorder and should be corrected if present. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment".)

Patients on kidney replacement therapy — Hypophosphatemia is extremely common in patients receiving continuous kidney replacement therapy (CKRT) using dialysate and replacement solutions that lack phosphate supplementation. Such patients will often require intermittent therapy with IV phosphate solutions, and we generally follow an IV phosphate repletion strategy as outlined above (see 'Intravenous dosing' above). These patients will continue to develop recurrent hypophosphatemia while they are requiring CKRT; thus, serial phosphorus measurements are necessary in this population. An alternative strategy for CKRT-mediated hypophosphatemia is to change the dialysate and/or replacement solutions to phosphate-containing formulations. (See "Prescription of continuous kidney replacement therapy in acute kidney injury in adults".)

While hypophosphatemia is less common in patients receiving intermittent dialysis therapies, it may still be observed in this population. This is particularly the case in individuals undergoing chronic dialysis therapy in the setting of concurrent malnutrition, aggressive phosphate binder therapy, intestinal phosphate losses (eg, chronic diarrhea or ostomy), or individuals with significant residual urine output.

X-linked hypophosphatemia and tumor-induced osteomalacia — X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO) are disorders that are characterized by renal phosphate wasting mediated by excess fibroblast growth factor 23 (FGF23) activity. The treatment of these disorders is discussed in detail separately. (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Fluid and electrolyte disorders in adults".)

SUMMARY AND RECOMMENDATIONS

●General principles – Hypophosphatemia is defined as a serum phosphorus concentration that is below the age-appropriate normal range (eg, less than 2.5 mg/dL [0.81 mmol/L] in adults). Hypophosphatemia can be induced by decreased net intestinal absorption, increased urinary phosphate excretion, or acute movement of extracellular phosphate into cells. (See 'Introduction' above.)

●Evaluation – In patients with hypophosphatemia, we take the following approach to evaluation:

•Exclude pseudohypophosphatemia – Spurious hypophosphatemia (pseudohypophosphatemia) may occur in certain clinical settings (eg, paraproteins or medications that interfere with the phosphate assay) and should be excluded to avoid unnecessary testing and inappropriate treatment of hypophosphatemia. (See 'Exclude pseudohypophosphatemia' above.)

•History and initial laboratory testing – Patients with true hypophosphatemia should be evaluated to identify the underlying cause, which is usually apparent from the history (table 1). In patients with unexplained persistent hypophosphatemia, we review the patient's medications to assess for drugs that can cause hypophosphatemia (table 2), review dietary history to assess for malnutrition, and review serum biochemical parameters, including bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, and magnesium levels. (See 'History and initial laboratory testing' above.)

•Assess urinary phosphate excretion – If the cause of hypophosphatemia is still not apparent, we measure urinary phosphate excretion to identify excess renal phosphate excretion. Phosphate excretion can be assessed with either a quantitative timed urine collection or by calculation of the fractional excretion of filtered phosphate (FEPO4) from a random urine specimen.

-A 24-hour urine phosphate excretion less than 100 mg or a FEPO4 less than 5 percent indicates appropriately low renal phosphate excretion, suggesting that the hypophosphatemia is caused by internal redistribution (eg, refeeding syndrome, acute respiratory alkalosis) or decreased intestinal absorption (eg, chronic antacid therapy, steatorrhea). (See 'Low phosphate excretion' above.)

-A 24-hour urine phosphate excretion greater than or equal to 100 mg or a FEPO4 greater than or equal to 5 percent indicates renal phosphate wasting, suggesting that the hypophosphatemia is caused by excess production of phosphaturic hormones (eg, hyperparathyroidism, increased circulating concentrations of fibroblast growth factor 23 [FGF23]) or a variety of other conditions. (See 'Inappropriately high phosphate excretion' above.)

●Treatment – Treatment of the underlying cause of hypophosphatemia is sufficient to resolve the hypophosphatemia in many cases. For patients with hypophosphatemia and a serum phosphorus less than 2 mg/dL (0.64 mmol/L), we suggest phosphate repletion (Grade 2C). Our approach to phosphate repletion is as follows (algorithm 1):

•If the serum phosphorus is <1 mg/dL (0.32 mmol/L), we treat with intravenous (IV) phosphate (table 3). We switch to oral phosphate when the serum phosphorus exceeds 1.5 mg/dL (0.48 mmol/L).

•If the serum phosphorus is 1 to 2 mg/dL (0.32 to 0.64 mmol/L), treatment varies with the presence or absence of overt symptoms of hypophosphatemia and the severity of hypophosphatemia:

-In asymptomatic patients, we give oral phosphate therapy (table 3). Many of these patients may have myopathy and weakness that are not clinically apparent.

-In symptomatic patients whose serum phosphorus is 1 to 1.5 mg/dL (0.32 to 0.48 mmol/L), we treat with IV phosphate and switch to oral phosphate (table 3) when the serum phosphorus exceeds 1.5 mg/dL (0.48 mmol/L).

-In symptomatic patients whose serum phosphorus is >1.5 to 2 mg/dL (0.48 to 0.64 mmol/L), we treat with oral phosphate therapy (table 3).

•We stop phosphate repletion when the serum phosphate is ≥2 mg/dL (0.64 mmol/L) unless there is an indication for chronic therapy such as persistent urinary phosphate wasting. (See 'Approach to repletion' above.)

ACKNOWLEDGMENT — The authors and UpToDate thank Dr. Zalman Agus, who contributed to earlier versions of this topic review.