Hyperphosphataemia in Chronic Kidney Disease

Hyperphosphataemia in chronic kidney disease is serum phosphate over the laboratory upper limit (about 1.5 mmol/L in adults), and in dialysis patients over the target of 1.7 mmol/L. It arises when phosphate intake and release from bone exceed renal and dialytic clearance, usually at eGFR below 30 mL/min/1.73 m². Conventional haemodialysis removes only about 800 to 1000 mg of phosphate in each session, far less than dietary absorption. FGF23 and parathyroid hormone maintain normal phosphate until late stages by increasing phosphaturia.

Consequences

• Secondary hyperparathyroidism, suppression of calcitriol, vascular and valvular calcification, calciphylaxis, left ventricular hypertrophy, bone disease and fractures, pruritus, and mortality (risk rises when phosphate exceeds 1.8 mmol/L).

Drivers: high intake of processed food (phosphate additives are over 90% absorbed, compared with 40 to 60% from animal protein and 20 to 40% from plants), reduced clearance, binder non-adherence, short or infrequent dialysis, bone resorption, acidosis, catabolism, and vitamin D analogues.

• Usually asymptomatic; detected on blood tests.
• Pruritus, red eyes (conjunctival calcium phosphate deposits), bone and joint pain, periarticular calcification.
• Tumoral calcinosis, vascular calcification, calcific uraemic arteriolopathy.
• Acute marked hyperphosphataemia: hypocalcaemia with tetany, seizures and arrhythmia (tumour lysis syndrome, rhabdomyolysis, sodium phosphate enema or oral phosphate preparations in chronic kidney disease, lactic acidosis, diabetic ketoacidosis).

Red flags

• Phosphate above 2.5 mmol/L with hypocalcaemia and symptoms: acute phosphate load.
• Painful necrotic skin lesions (calciphylaxis).
• Phosphate persistently above 2.0 mmol/L despite binders and adequate dialysis: look for non-adherence, bone resorption, hypoparathyroidism, hypercatabolism.

• Fasting or pre-dialysis serum phosphate, taken at the same point in the dialysis week (after the long interval, before dialysis) to assess true exposure. Repeat monthly in dialysis, every 1 to 3 months in G5, every 3 to 6 months in G4.
• Corrected calcium, parathyroid hormone, alkaline phosphatase, bicarbonate, 25-hydroxyvitamin D, magnesium.
• Dietary history, medication list (phosphate binders, vitamin D analogues, phosphate enemas, laxatives), binder timing and adherence, dialysis adequacy (Kt/V, session length and frequency).
• Exclude pseudohyperphosphataemia: paraproteinaemia, haemolysed samples, hyperlipidaemia, hyperbilirubinaemia; confirm on repeat sample.

Differential diagnosis (cause of high phosphate)

• Acute: tumour lysis, rhabdomyolysis, lactic acidosis, diabetic ketoacidosis, phosphate enemas or laxatives, haemolysis.
• Endocrine: hypoparathyroidism, pseudohypoparathyroidism, acromegaly, vitamin D toxicity, thyrotoxicosis.
• Familial tumoral calcinosis (FGF23, GALNT3 or KL mutations).

First line: diet and dialysis

• Restrict dietary phosphorus to 800 to 1000 mg daily with protein intake kept at 0.8 g/kg daily (do not allow protein malnutrition). Avoid processed foods, cola, and additives listing phosphate; prefer plant sources and fresh foods; boiling reduces phosphate.
• Dialysis intensification: longer sessions (at least 4 hours three times weekly), more frequent or nocturnal haemodialysis, haemodiafiltration, or increased exchanges in peritoneal dialysis. Hypophosphataemia can occur with daily dialysis; supplement dialysate phosphate if needed.

Phosphate binders (taken at the start of meals; titrate to phosphate 1.1 to 1.7 mmol/L in dialysis, towards normal in non-dialysis disease)

• Sevelamer carbonate 800 mg three times daily with meals; increase by 800 mg with each meal every 2 to 4 weeks; maximum about 13 g daily. Gastrointestinal side effects; advantages include lowering LDL cholesterol and no calcium load. Reduces absorption of ciprofloxacin and mycophenolate; give ciprofloxacin at least 2 hours before or 6 hours after sevelamer.
• Calcium carbonate with meals, 500 mg elemental calcium in each dose; keep total elemental calcium from binders to 1.5 g daily; avoid if calcium is above 2.5 mmol/L, in adynamic bone or vascular calcification.
• Lanthanum carbonate 500 mg chewed with meals, increased by 750 mg daily every 2 to 3 weeks to a maximum of 3750 mg daily.
• Sucroferric oxyhydroxide 500 mg chewed with each meal (start 1.5 g daily, maximum 3 g daily); discolours stools.
• Ferric citrate 1 g with each meal, titrating by 1 to 2 g daily at weekly intervals to a maximum of 12 g daily; raises ferritin and transferrin saturation.
• Short term only (up to 4 weeks) for refractory severe hyperphosphataemia: aluminium hydroxide 600 mg three times daily with meals, with an aluminium level checked afterwards; avoid long term.
• Combine two binders of different classes if phosphate remains over target; use the lowest effective pill burden to support adherence.

Treat contributors. Vitamin D analogues increase intestinal phosphate absorption; reduce the dose if phosphate is high and calcium is normal. Correct acidosis. Control parathyroid hormone, since cinacalcet and etelcalcetide reduce phosphate.

Acute severe hyperphosphataemia with symptomatic hypocalcaemia

• Calcium gluconate 10% 10 mL intravenously over 10 minutes only for tetany, seizures or arrhythmia (calcium phosphate precipitation risk).
• Urgent haemodialysis, high blood flow, for phosphate above 3.0 mmol/L or symptoms. Avoid sodium phosphate enemas and bowel preparations in chronic kidney disease.

Monitoring. Phosphate monthly in dialysis; calcium and parathyroid hormone every 3 months; adjust the binder dose as meals change.

Referral and escalation. Dietitian review for all patients with phosphate above 1.5 mmol/L; nephrology for refractory disease; urgent review for acute high level hyperphosphataemia.

Special groups

• Children: calcium carbonate with feeds; sevelamer carbonate for age at least 6 years; avoid lanthanum before growth completes.
• Pregnancy: calcium carbonate only; avoid lanthanum and sevelamer if possible.
• Transplant recipients: hypophosphataemia, rather than excess, usually follows engraftment.