Phosphate Binders in Chronic Kidney Disease

Phosphate binders lower the absorption of dietary phosphate in chronic kidney disease, where falling excretion raises serum phosphate and drives secondary hyperparathyroidism, vascular calcification and mortality. Treatment aims to move phosphate toward the normal range, about 0.8 to 1.5 mmol/L (2.5 to 4.6 mg/dL), without causing hypercalcaemia, and starts with dietary advice before or with a binder.

Dietary phosphate. Inorganic phosphate additives in processed foods and cola drinks are absorbed almost completely, while plant phosphate is absorbed less. Advise reducing additives before restricting protein.

Binding. Binders act only in the gut, so they must be taken with meals and snacks that contain phosphate.

Calcium load. Calcium-based binders add absorbed calcium. Limit elemental calcium from binders to about 1500 mg daily.

Choice.

• Normal or low calcium, no vascular calcification: calcium carbonate or calcium acetate.

• High or high-normal calcium, vascular calcification, low parathyroid hormone or adynamic bone: sevelamer carbonate, lanthanum carbonate, or an iron-based binder.

• Iron deficiency in dialysis: ferric citrate or sucroferric oxyhydroxide may serve both purposes.

• Short-term severe hyperphosphataemia: aluminium hydroxide for no more than 4 weeks, then stop.

Avoid. Long-term aluminium (bone disease, encephalopathy, anaemia) and magnesium-containing binders in advanced disease.

Special groups.

• Children: dose by age and phosphate target, preferring calcium carbonate or sevelamer, with growth monitoring.

• Pregnancy: calcium carbonate is preferred. Data for other binders are limited.

• Older adults: tablet size and constipation limit use, so choose chewable or powder forms.

• East Africa: where calcium-based binders are the only ones available, check calcium often and limit the dose, and counsel on processed foods and cola drinks.

• Calcium carbonate: start 500 mg elemental calcium (a 1.25 g tablet) with each main meal, chewed. Increase every 2 weeks to the target, within the calcium limit.

• Calcium acetate: 1334 mg (two 667 mg capsules) with each meal, increased by 667 mg each meal every 2 weeks.

• Sevelamer carbonate: 800 mg three times daily with meals when phosphate is under 2.4 mmol/L, 1600 mg three times daily when over 2.4 mmol/L. Increase by 800 mg each meal every 2 weeks.

• Lanthanum carbonate: 500 mg three times daily, chewed with meals, increased by 750 mg daily every 2 to 3 weeks. Usual range 1500 to 3000 mg daily, maximum 3750 mg.

• Sucroferric oxyhydroxide: 500 mg three times daily, chewed, usual range 1500 to 2000 mg daily, maximum 3000 mg.

• Ferric citrate: 2 tablets (1 g) three times daily with meals, increased by 1 to 2 tablets daily every week, maximum 12 tablets daily.

Interactions. Binders reduce absorption of levothyroxine, ciprofloxacin, doxycycline and mycophenolate. Give levothyroxine 4 hours apart. Give ciprofloxacin at least 2 hours before or 6 hours after a binder.

Monitoring. Check phosphate and corrected calcium every 2 to 4 weeks during titration, then every 3 months, with parathyroid hormone and alkaline phosphatase every 3 to 6 months. Review bowel function and pill burden.

Stop rules. Stop or reduce a calcium-based binder when corrected calcium is over 2.55 mmol/L, and switch to a non-calcium binder. Stop aluminium after 4 weeks. Stop sevelamer or lanthanum for bowel obstruction or severe constipation.

Referral and escalation. Refer when phosphate stays over 2.0 mmol/L despite diet and a binder, when parathyroid hormone is markedly raised, when calciphylaxis or progressive vascular calcification is suspected, or when dialysis adequacy is in doubt.

Common errors. Giving binders away from meals, using them with fasting patients, ignoring total calcium load, and giving levothyroxine or ciprofloxacin at the same time.