Phosphate Binders

Phosphate binders are taken with meals to bind dietary phosphate in the gut, lowering serum phosphate in advanced chronic kidney disease. They are used with dietary phosphate restriction and adequate dialysis.

Mechanism. They form insoluble, non-absorbable complexes with phosphate in the gut lumen, which are excreted in the stool. Tenapanor, an NHE3 inhibitor, reduces paracellular phosphate absorption.

Pharmacokinetics. Most binders are not absorbed. Calcium, aluminium, lanthanum and iron can be absorbed in small amounts.

Differences. Calcium-based binders are cheap but add to vascular calcification risk. Non-calcium binders are costly. Aluminium causes dementia, bone disease and anaemia, and is limited to very short use.

• Indication: persistent hyperphosphataemia (over 1.45 mmol/L, or 4.5 mg/dL) despite diet advice and adequate dialysis.
• Timing: with or immediately after each meal containing phosphate, and omitted with fasting.
• Choice: calcium-based first where calcium is normal or low; non-calcium where there is hypercalcaemia, vascular calcification or low PTH.
• Titration: change one agent at a time every 2 to 4 weeks, aiming for phosphate in the normal range (0.8 to 1.45 mmol/L).
• Dietary restriction: limit processed foods and additives, which have the greatest phosphate absorption.

Special groups. Pregnancy: calcium carbonate is used; limited data for others. Breastfeeding: calcium-based are acceptable. Children: calcium-based first-line. Older adults: pill burden and constipation. Kidney impairment: the target population. Liver impairment: no adjustment. Regional: dialysis access is limited, so calcium carbonate is often the only available agent; avoid aluminium except in short courses.

Adverse effects. Constipation (calcium, sevelamer), nausea and vomiting (lanthanum), hypercalcaemia (calcium-based), diarrhoea and dark stools (iron-based), metabolic acidosis (sevelamer hydrochloride), hypophosphataemia, and aluminium toxicity.

Interactions. Binders reduce absorption of ciprofloxacin (give it 2 hours before or 6 hours after), levothyroxine (4 hours apart), mycophenolate, doxycycline and ciclosporin. Calcium raises hypercalcaemia risk with vitamin D analogues.

Monitoring. Phosphate and calcium every 2 to 4 weeks during titration, then monthly to 3 monthly; PTH; bicarbonate; stool habit.

Referral and escalation. Phosphate over 2.0 mmol/L, calcium over 2.6 mmol/L, or vascular calcification.