Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

lack of sunlight

1st line – ultraviolet radiation exposure

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ACUTE
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lack of sunlight
1st line – 

ultraviolet radiation exposure

Exposure to sunlight depends on physical factors (e.g., geographic latitude, season, weather, time of day) and personal factors (e.g., skin pigmentation, body surface area exposed, sunscreen use).[3][12][15]

For a white person, exposure to sunlight at most latitudes for no more than 10 to 15 minutes/day between 10 a.m. and 3 p.m., on arms and legs or hands, face, and arms, during the spring, summer, and fall, provides adequate vitamin D. Ultraviolet-B radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D.[2] Limited exposure of bare skin to sunlight should be followed by the application of a sunscreen with an SPF of at least 15 to prevent damaging effects due to excessive exposure to sunlight and to prevent sun burning.

Consider – vitamin D supplementation

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ACUTE
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lack of sunlight
Consider – 

vitamin D supplementation

Treatment recommended for SOME patients in selected patient group

If there is concern that it may be difficult for the patient to receive sufficient ultraviolet radiation exposure, vitamin D-containing dietary supplements may be given.

There are various multivitamin supplements that contain either ergocalciferol or cholecalciferol.

In the US, a number of dairy products, juice and juice drinks, and cereals are fortified with vitamin D, and consumption of these should be encouraged as part of a balanced diet in individuals at risk of vitamin D deficiency.

Primary options

ergocalciferol (vitamin D2): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

OR

cholecalciferol (vitamin D3): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

Consider – calcium supplementation

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ACUTE
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lack of sunlight
Consider – 

calcium supplementation

Treatment recommended for SOME patients in selected patient group

If there is evidence of, or a risk of, poor dietary intake of calcium, then calcium supplements may also be appropriate.

Primary options

calcium carbonate: children: 210-1300 mg/day orally given in 3-4 divided doses; adults: 1000-1500 mg/day orally given in 3-4 divided doses

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malabsorption-related

1st line – optimized management of underlying disease

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ACUTE
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malabsorption-related
1st line – 

optimized management of underlying disease

Treatment of the underlying disease should also be optimized to help improve absorption. Depending on the cause, this may involve a gluten-free diet for celiac disease, a lactose-free diet for lactose intolerance, protease and lipase supplements for pancreatic insufficiency, or corticosteroids and anti-inflammatory agents for inflammatory bowel disease.

Consider – ultraviolet radiation exposure

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ACUTE
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malabsorption-related
Consider – 

ultraviolet radiation exposure

Treatment recommended for SOME patients in selected patient group

Patients with intestinal malabsorption syndromes are often vitamin D deficient.

As the metabolic pathways in the liver and the kidneys are not compromised in these patients, the best method to correct vitamin D deficiency is to encourage sensible exposure to sunlight or ultraviolet-B-emitting light source/tanning bed.[2] 

Consider – vitamin D supplementation

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ACUTE
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malabsorption-related
Consider – 

vitamin D supplementation

Treatment recommended for SOME patients in selected patient group

Augmentation with oral supplements of vitamin D may be required.

Estimates are that the body uses an average of 3000 to 5000 international units of cholecalciferol per day.[45]

In the absence of adequate sun exposure, it is estimated 1000 international units of cholecalciferol is needed to maintain a healthy 25-hydroxyvitamin D level of at least 30 nanograms/mL.

One meta-analysis comparing ergocalciferol and cholecalciferol has shown cholecalciferol to be more effective in maintaining serum concentrations of 25-hydroxyvitamin D.[13] 

Vitamin D or its analogs serve to help increase gastrointestinal calcium absorption, thereby reducing parathyroid hormone levels. Intramuscular administration is sometimes used, as these patients have malabsorption from the gastrointestinal tract; however, this formulation is not available in the US and some other countries.

Primary options

ergocalciferol (vitamin D2): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

OR

cholecalciferol (vitamin D3): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

Consider – calcium supplementation

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ACUTE
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malabsorption-related
Consider – 

calcium supplementation

Treatment recommended for SOME patients in selected patient group

Patients with intestinal malabsorption syndromes are often calcium deficient.

Primary options

calcium carbonate: children: 45-65 mg/kg/day orally given in 4 divided doses; adults: 2-4 g/day orally given in 3-4 divided doses

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CKD stages 3 to 5D

1st line – dietary phosphate restriction

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ACUTE
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CKD stages 3 to 5D
1st line – 

dietary phosphate restriction

In patients with chronic kidney disease (CKD), dietary phosphorus should be restricted to 800 to 1000 mg/day in adults or to Dietary Reference Intake (DRI) for age when serum phosphate and plasma levels of parathyroid hormone are elevated above the the normal reference range.[1]​​

Serum phosphorus levels should be monitored monthly in stage 5 CKD and every 3 months in stages 3 or 4 following initiation of dietary phosphorus restriction.

Consider – phosphate binder

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ACUTE
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CKD stages 3 to 5D
Consider – 

phosphate binder

Treatment recommended for SOME patients in selected patient group

If phosphorus or parathyroid hormone levels cannot be controlled within the target range despite dietary phosphorus restriction, phosphate binders should be prescribed.[48]

Either calcium-based phosphate binders, iron-based phosphate binders (e.g., iron sucrose, sucroferric oxyhydroxide), or others (e.g., sevelamer, lanthanum) are effective.[57] Combination of different types may be required under specialist supervision. 

Aluminum-based phosphate binders (e.g., aluminum hydroxide) are an alternative, but may increase the risk of adynamic bone disease due to the toxic effects of aluminum on bone.[1]​ They may be used in adolescents and adults for a single course of short-term therapy (4 weeks) if serum phosphorus levels remain severely elevated despite the use of other phosphate binders. Use of citrate-based products must be avoided in patients taking aluminum binders, as this has been shown to lead to enhanced absorption and cases of neurologic toxicity.[59]

After initial treatment, the aluminum-based phosphate binder should be replaced by a different phosphate binder. In patients receiving dialysis (with persistent, severely elevated phosphorus levels), the dialysis prescription should also be modified to increase dialytic phosphate removal.[59]

In infants and young children, calcium-based phosphate binders should be used as primary therapy; other types of phosphate binders may be used in older children.

In patients receiving dialysis who have severe vascular and/or other soft-tissue calcification, noncalcium-based phosphate binders are preferred.[58] 

Primary options

calcium acetate: children: consult specialist for guidance on dose; adults: 1334 mg orally with each meal, adjust dose according to serum phosphorus level, maximum 2868 mg/dose

OR

sevelamer hydrochloride: children and adults: consult specialist for guidance on dose

OR

lanthanum: children and adults: consult specialist for guidance on dose

OR

iron sucrose: children and adults: consult specialist for guidance on dose

OR

sucroferric oxyhydroxide: children and adults: consult specialist for guidance on dose

Secondary options

aluminum hydroxide: children and adults: consult specialist for guidance on dose

Plus – vitamin D supplementation

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ACUTE
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CKD stages 3 to 5D
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with low vitamin D
Plus – 

vitamin D supplementation

Treatment recommended for ALL patients in selected patient group

Vitamin D deficiency in chronic kidney disease is corrected using treatment strategies recommended for the general population.[1]​​[37] 

If the serum level of 25-hydroxyvitamin D is <30 nanograms/mL, vitamin D supplementation with ergocalciferol or cholecalciferol should be initiated.[6][13][37][63] 

Following initiation of vitamin D therapy, dose adjustments should be made in light of serum calcium and phosphorus levels. Serum levels of corrected total calcium and phosphorus should be measured at least every 3 months.

Once the patient is replete of 25-hydroxyvitamin D, continue supplementation with a vitamin D-containing multivitamin preparation or a low dose of vitamin D, and check serum levels of 25-hydroxyvitamin D annually.[15]

Calcifediol, a prohormone of calcitriol, is a more potent vitamin D3 supplementation.[64]​ It is approved in the US for the management of SHPT in patients with CKD stages 3 to 4 and serum total 25-hydroxyvitamin D levels <30 nanograms/mL.[65]

Primary options

ergocalciferol (vitamin D2): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

OR

cholecalciferol (vitamin D3): children and adults: dose depends on serum 25-hydroxyvitamin D levels; consult specialist for guidance on dose

OR

calcifediol: adults: 30 micrograms orally once daily at bedtime initially, may increase to 60 micrograms once daily after 3 months if serum intact PTH level is above the treatment goal

Plus – vitamin D sterol/analog

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ACUTE
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CKD stages 3 to 5D
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with normal serum 25-hydroxyvitamin D
Plus – 

vitamin D sterol/analog

Treatment recommended for ALL patients in selected patient group

The target range for parathyroid hormone (PTH) in patients on dialysis is 2 to 9 times the upper limit of normal for the PTH assay.[1]​ The target range for chronic kidney disease stages 3 to 5, predialysis, is undefined, but severe and progressive SHPT in this group can be treated following the same principles.

Therapy with an active oral vitamin D sterol (calcitriol) or a synthetic vitamin D analog (e.g., doxercalciferol, paricalcitol) is indicated when modifiable factors (hyperphosphatemia, hypocalcemia, vitamin D deficiency) have been addressed and plasma levels of PTH continue to rise toward the upper limit of the target range.[1]​​[37] 

Treatment with a vitamin D sterol/analog should be undertaken only in patients with serum levels of 25-hydroxyvitamin D, corrected total calcium, and phosphorus within the normal range.

During therapy with a vitamin D sterol/analog, serum levels of calcium and phosphorus should be monitored at least every month after initiation of therapy for the first 3 months, then at least every 3 months thereafter. Plasma PTH levels should be measured at least every 3 months for 6 months, and every 3 months thereafter.

If serum levels of PTH decrease to values below the target range, vitamin D sterol/analog therapy should be stopped until serum PTH is within the target range; treatment may then be resumed at one half of the previous dose of vitamin D sterol/analog. If the lowest daily dose of the vitamin D sterol/analog is being used, dosing should be reduced to alternate days. 

If there is hypercalcemia, vitamin D sterol/analog therapy should be stopped until serum calcium returns to normal, and then resumed at one half of the previous dose. If the lowest daily dose of the vitamin D sterol/analog is being used, dosing should be reduced to alternate days.

If there is hyperphosphatemia, vitamin D therapy should be stopped and a phosphate binder initiated, or the phosphate binder dose increased, until the level of serum phosphorus is normal, at which point the prior dose of vitamin D sterol/analog should be resumed.

If serum levels of PTH fail to decrease by at least 30% after the initial 3 months of therapy, and serum levels of calcium and phosphorus are within the normal range, the dose of vitamin D sterol/analog should be increased by 50%. Serum levels of PTH, calcium, and phosphorus must be measured monthly for 3 months thereafter.

Primary options

calcitriol: children: consult specialist for guidance on dose; adults: 0.25 micrograms orally once daily initially, adjust dose according to serum PTH, calcium, and phosphorus levels

Secondary options

doxercalciferol: children and adults: dose based on serum PTH level; consult specialist for guidance on dose

OR

paricalcitol: children and adults: dose based on serum PTH level; consult specialist for guidance on dose

Plus – reduction of calcium load

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ACUTE
|
CKD stages 3 to 5D
|
with hypercalcemia
Plus – 

reduction of calcium load

Treatment recommended for ALL patients in selected patient group

Serum levels of corrected total calcium should be maintained within the normal range for the laboratory used.[1]​ 

If there is hypercalcemia, the use of calcium-based phosphate binders should be restricted and therapy switched to a noncalcium-based phosphate binder (e.g., sevelamer, lanthanum, or an iron-based phosphate binder).[1]​ 

The dose of vitamin D therapy should be reduced or therapy discontinued until the serum levels of corrected total calcium return to the target range.[1]​ 

In patients treated with dialysis, the dialysate calcium concentration should be targeted to 2.5 to 3.0 mEq/L (1.25 to 1.50 mmol/L).

Primary options

sevelamer hydrochloride: children and adults: consult specialist for guidance on dose

OR

lanthanum: children and adults: consult specialist for guidance on dose

OR

iron sucrose: children and adults: consult specialist for guidance on dose

OR

sucroferric oxyhydroxide: children and adults: consult specialist for guidance on dose

Plus – calcium salt and/or vitamin D sterol

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ACUTE
|
CKD stages 3 to 5D
|
with hypocalcemia
Plus – 

calcium salt and/or vitamin D sterol

Treatment recommended for ALL patients in selected patient group

Hypocalcemia is a classical feature of untreated chronic kidney disease and contributes to the pathogenesis of SHPT. It may also develop in the context of calcimimetic treatment. Patients with hypocalcemia should receive therapy to increase serum calcium levels if significant or symptomatic.[1]​​

Therapy for hypocalcemia should be individualized and include calcium salts such as calcium carbonate or calcium acetate orally, or calcium gluconate or calcium chloride parenterally, and/or an oral vitamin D sterol/analog.

Adjust dose of calcium salt according to serum calcium levels.

Primary options

calcium carbonate: children: 45-65 mg/kg/day orally given in 4 divided doses; adults: 2-4 g/day orally given in 3-4 divided doses

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or

calcium gluconate: children: 200-500 mg/kg/day intravenously by infusion or given in 4 divided doses; adults: 2-15 g/day intravenously by infusion or given in 4 divided doses

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-- AND / OR --

calcitriol: children: consult specialist for guidance on dose; adults: 0.25 micrograms orally once daily initially, adjust dose according to serum PTH, calcium, and phosphorus levels

or

doxercalciferol: children and adults: dose based on serum PTH level; consult specialist for guidance on dose

or

paricalcitol: children and adults: dose based on serum PTH level; consult specialist for guidance on dose

Plus – parathyroidectomy or calcimimetic

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ACUTE
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CKD stages 3 to 5D
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with persistently elevated PTH
Plus – 

parathyroidectomy or calcimimetic

Treatment recommended for ALL patients in selected patient group

If the parathyroid hormone (PTH) level is above 9 times the upper limit of normal in patients on dialysis, and there is hypercalcemia and/or hyperphosphatemia, despite optimization of medical therapy (to control serum phosphorus, calcium, and vitamin D), parathyroidectomy or calcimimetic therapy is indicated.[1]​​

Effective surgical therapy can be accomplished by subtotal parathyroidectomy or total parathyroidectomy with parathyroid tissue auto-transplantation.[1]​​[92]

If surgical parathyroidectomy is considered to have a high risk of complications, calcimimetic medications can be used. Calcimimetics can also be used as a bridging therapy to parathyroidectomy.

In patients who undergo parathyroidectomy, ionized calcium should be measured every 4 to 6 hours for the first 48 to 72 hours after surgery, and then twice daily until stable.

If the blood levels of ionized or corrected total calcium fall below normal (<3.6 mg/dL corresponding to corrected total calcium of 7.2 mg/dL), a calcium gluconate infusion should be initiated at a rate of 1 to 2 mg elemental calcium/kg body weight/hour and adjusted to maintain an ionized calcium in the normal range (4.6 to 5.4 mg/dL). A 10 mL ampule of 10% calcium gluconate contains 90 mg of elemental calcium. The calcium infusion should be gradually reduced when the level of ionized calcium reaches the normal range and remains stable. When oral intake is possible, the patient should receive calcium carbonate 1 to 2 grams, 3 times a day, and calcitriol of up to 2 micrograms/day, and these therapies should be adjusted as necessary to maintain the level of ionized calcium in the normal range.

If the patient was receiving phosphate binders prior to surgery, this therapy may need to be discontinued or reduced as dictated by the levels of serum phosphorus.

Calcimimetic medications, such as cinacalcet, bind to calcium-sensing receptors (CaSR) and increase their sensitivity to extracellular ionized calcium.[67] This results in decreases in PTH, and thus calcium and phosphate levels.[63]

The effect on PTH levels can be seen as quickly as 2 to 4 hours after administration.[68]

Etelcalcetide is a second-generation calcimimetic and CaSR agonist, which may be used where treatment with a calcimimetic is indicated but cinacalcet is not tolerable or there is poor compliance.[86][87] It is given intravenously (rather than orally like cinacalcet) and has a longer half-life than cinacalcet.

Primary options

cinacalcet: children: consult specialist for guidance on dose; adults: 30 mg orally once daily initially, increase dose according to serum PTH level, maximum 180 mg/day

Secondary options

etelcalcetide: adults: 5 mg intravenously three times weekly at the end of hemodialysis treatment, adjust dose according to PTH level and corrected serum calcium response, maintenance dose ranges from 2.5 to 15 mg three times weekly

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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