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Management of hyperphosphataemia of chronic kidny disease

Presented byPharmacist/ Eman Youssif

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Role of calcium balance and phosphorus retention

• Hypocalcaemia and phosphorus retention has a role in secondary hyperparathyroidism and renal osteodystrophy.

1- Aluminum based phosphate binders.2- Calcium based phosphate binders.3- Non-aluminum, non-calcium based phosphate

binders.4- magnesium based phosphate

binders(experimentally).

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Calcium based phosphate binding agents

Relatively benign.Requires large daily calcium dose.Ingestion of large amount causes positive

calcium balance(hyper-calcaemia, progressive metastatic calcification, and a dynamic bone disorder)

Ca x p increases the risk of cardiac calcification in the dialysis patients.

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The phosphate binding capacity of CCP binders is not as efficient as aluminum containing phosphate binders.

To avoid metastatic calcification recommendations to limit calcium intake to less than 2000mg/day(of this amount 1500 may be from phosohate binder and 500 from dietary source).

CCP should be re-evaluated if serum calcium increases above 10.2 mg/dl or if Ca x p is greater than 55 mg2/dl2

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Different calcium salts differ in the amount of elemental calcium as well as side effects.

Calcium citrate is avoided in KD as it increases acidity(enhances aluminum absorption).

Calcium actate :• (phos-lo 667)one tablet contain 169mg

elemental calcium.• Dose: 2-3 tablets with meals.

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• It contain lower amount of elemental calcium than calcium carbonate(25% VS 40% respectively).

• Calcium acetat is more efficient phosphorus binder.

• Increasing binding of calcium to phosphorus with acetate salt is due to

*Decreased GIT absorption of calcium. *Increased solubility and dissociation of

acetate moiety.

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• Calcium acetate and calcium carbonate are given in doses that are equivalent regard to elemental calcium content.

• The acetate salt not only lowers the phosphorus concentration more effectively , but also associated with lower incidence of hypercalcemia than the carbonate salt.

• The problem is calcium acetate formulation is unpalatable and cause uncomfortable GIT effect, this problem has led to poor compliance among patients.

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• Any of the calcium salts react with anti-microbial agents(fluroquinolones and tetracyclins) so, it should be administered 1 hr before or 3 hr after calcium products.

• Spacing between calcium salts and iron is recommended for better iron absorption.

• H2 blockers and PPI affects the calcium binding to phosphorus, so spacing is advisable.

• Calcium carbonate dose:0.8-2g elemental calcium with meals.

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Aluminum based phosphate binding agents

Efficient binding to phosphate.Chemically able to form tight, insoluble

complex with phosphate.Reserved for situations in which phosphorus

concenteration is very high(7.0 mg/dl)and Ca x p is greater than(55mg2/dl2

Kidney is the primary route of aluminum excretion.

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Ingestion of large doses over extended period of time was found to show absorption.

Uremic stat enhance absorption and retention of aluminum to toxic level(encephalopathy, osteomalacia, decreased responsiveness to erythropoietic agents, constipation).

Aluminum concentration should be assessed and should be below 20µg/dl.

Aluminum containing binders used for a maximum 30 days.

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• Aluminum hydroxide dose: 300-600mg with meals.

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Non-aluminum,non-calcium based phosphate binders

• Lanthanum salts(lanthanum carbonate).• Sevelamer HCl.

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Lanthanum salts

Lanthanum is a rare earth metal, found in trace amount in the body

Lanthanum cations bind phosphate anions to form an insoluble salt that is poorly absorbed by GIT.

Lanthanum chloride shows some solubility and absorption, while lanthanum carbonate shows less solubility.

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After long term use in rates, accumulation in body organs occurred (liver, lung, and kidny tissues).

Long term safety studies have not been reported.

Not evaluated for drug-drug interactions.Dose:500-1000mg.

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sevelamerHCl

Bind to phosphorus in exchange to chloride ion.

Controls serum phosphorus and Ca x P in dialysis patients.

Minimum impact on serum calcium level and low incidence of side effects.

Positive changes in blood lipids occurred during treatment(lowers LDL, raises HDL).

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Lowers risk of hospitalization.Adverse effects ay include: *Nausea. *Vomiting. *Bloating. *Constipation. *Increased risk of colonic obstruction and

perforation. *Increased incidence metabolic acidosis associated

with exchange of chloride ion for short chain fatty acid ions.

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• *Insoluble in water, expands upon contact with water, tablets or capsules should not be crushed, so it is in-approprite for alternative routes of administration(naso-gastric, oral-gastric or per-cutaneous entero-gastric feeding tubes).

• *significantly decrease the bio-availability of ciprofloxacin.

• *no sufficient study on drug-drug interaction.

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• sevelamer HCl dose: 800-1600mg with meals.

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• These medications: - given with food(meals/snaks) to bind the

intestinal phosphorus from dietary intake before it's absorption.

- given routinely and multiple times a day. - phosphate binders from different classes may

be combined to achieve target concentration of phosphorus and calcium.

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Salivary phosphate binding chewing gum reduces hyperphosphatemia in dialysis patients

• A hyper phosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients.

• Adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyper-phosphatemia in HD patients.

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Thank you