What is the management for a patient with hyperphosphatemia, likely due to chronic kidney disease (CKD) or acute kidney injury (AKI)?

Management of Hyperphosphatemia

In patients with CKD G3a-G5D and progressively or persistently elevated serum phosphate, initiate dietary phosphate restriction to 800-1,000 mg/day first, then add phosphate binders starting with calcium-based agents (limiting elemental calcium to ≤1,500 mg/day), but switch to non-calcium binders if hypercalcemia, vascular calcification, or suppressed PTH (<150 pg/mL) develops. 1, 2

When to Initiate Treatment

Treatment should only be initiated for progressively or persistently elevated serum phosphate—not for prevention or single elevated values. 1, 2, 3

• Base treatment decisions on serial assessments of phosphate, calcium, and PTH levels considered together, not isolated measurements. 1, 2
• For CKD G3a-G5 (not on dialysis), lower elevated phosphate levels toward the normal range (2.7-4.6 mg/dL). 1
• For CKD G5D (dialysis patients), target serum phosphorus between 3.5-5.5 mg/dL, initiating binders when levels exceed 5.5 mg/dL. 2, 4
• Normophosphatemia is NOT an indication to start phosphate-lowering treatments—this reflects evidence that preventing hyperphosphatemia may cause more harm than benefit, particularly with calcium-based binders. 2, 3

Step 1: Dietary Phosphate Restriction

Limit dietary phosphate intake to 800-1,000 mg/day as the initial approach, adjusting based on protein needs to maintain adequate protein intake of 1-1.2 g/kg/day. 2, 4, 3

• Phosphate bioavailability varies dramatically by source: animal-based phosphate (40-60% absorbed), plant-based phosphate (20-50% absorbed), and inorganic phosphate in food additives (often >90% absorbed). 1, 2, 3
• Educate patients to avoid processed foods containing phosphate additives, which are highly absorbable and often unlabeled. 2, 5
• Dietary restriction alone is usually insufficient in most CKD patients and requires the addition of binders. 2, 3

Step 2: Phosphate Binders

For CKD G3a-G4 (Not on Dialysis)

Start with calcium-based phosphate binders (calcium acetate or calcium carbonate) when serum phosphorus exceeds 4.6 mg/dL despite dietary restriction. 2, 4, 3

• Limit elemental calcium from binders to ≤1,500 mg/day and total calcium intake (including dietary) to not exceed 2,000 mg/day. 1, 2, 4
• Restrict the dose of calcium-based binders to avoid excess calcium exposure, which may be harmful across all GFR categories of CKD. 1, 3

For CKD G5D (Dialysis Patients)

Either calcium-based binders or non-calcium binders can be used as primary therapy, but non-calcium binders (sevelamer, lanthanum carbonate, sucroferric oxyhydroxide) should be strongly preferred in specific high-risk situations. 2, 4

Absolute indications for non-calcium binders: 2, 4, 3

• Hypercalcemia (corrected serum calcium >10.2 mg/dL)
• Suppressed PTH (<150 pg/mL in two consecutive measurements)
• Severe vascular or soft-tissue calcifications
• Adynamic bone disease

Aluminum-Based Binders

Use aluminum-based binders only as short-term therapy (maximum 4 weeks, single course only) for severe hyperphosphatemia (>7.0 mg/dL), then switch to other agents due to toxicity concerns. 2, 4, 3

Step 3: Combination Therapy

If hyperphosphatemia persists (>5.5 mg/dL) despite monotherapy, combine calcium-based and non-calcium-based binders, which may yield additive benefits. 2, 3, 6

Step 4: Increase Dialytic Phosphate Removal

In patients with CKD G5D with persistent hyperphosphatemia despite binders, increase dialytic phosphate removal by considering more frequent or longer dialysis sessions. 1, 2, 3

• Use a dialysate calcium concentration between 1.25 and 1.50 mmol/L (2.5 and 3.0 mEq/L). 1, 2

Monitoring Targets

Maintain corrected total serum calcium in the normal range, preferably 8.4-9.5 mg/dL (lower end of normal) for dialysis patients, and avoid hypercalcemia in all CKD G3a-G5D patients. 1, 2, 3

• Maintain Ca × P product <55 mg²/dL². 2
• Monitor serum phosphorus levels monthly following initiation of phosphate binder therapy. 4
• Monitor serum calcium levels regularly to detect hypercalcemia, especially with calcium-based binders. 4
• Monitor PTH levels to avoid oversuppression when using calcium-based binders. 4

Management of Secondary Hyperparathyroidism

Patients with progressively rising or persistently elevated PTH above the upper normal limit should be evaluated for modifiable factors, including hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency—correcting hyperphosphatemia is a critical first step before addressing PTH directly. 1, 2, 3

• For CKD G5D, maintain intact PTH levels in the range of approximately 2-9 times the upper normal limit for the assay. 2
• For those requiring PTH-lowering therapy, use calcimimetics, calcitriol, or vitamin D analogs, or a combination. 2
• Do not routinely use calcitriol and vitamin D analogues in CKD G3a-G5 not on dialysis—reserve for patients with CKD G4-G5 with severe and progressive hyperparathyroidism. 1

Special Populations: Children

In children with CKD G3a-G5D, base the choice of phosphate-lowering treatment on serum calcium levels and maintain serum calcium in the age-appropriate normal range. 1, 2

• Sevelamer has proven efficacy and safety in pediatric patients, particularly when hypercalcemia is a concern. 4

Critical Pitfalls to Avoid

Do not use calcium-based binders in hypercalcemic patients or those with suppressed PTH (<150 pg/mL), as this worsens outcomes. 2, 3

• Excess calcium exposure from calcium-based binders may contribute to cardiovascular calcification across all stages of CKD. 1, 2, 3
• Patients with vascular or valvular calcification should be considered at highest cardiovascular risk, and this should guide management decisions—specifically favoring non-calcium binders. 2
• Overly aggressive PTH suppression can lead to adynamic bone disease—normal or low PTH levels in ESRD may indicate adynamic bone disease, which is also problematic. 2
• Patients on long-term calcium-based binder therapy should be assessed for signs of vascular calcification. 4

Drug Interactions with Sevelamer

Sevelamer can significantly reduce the bioavailability of several medications, requiring dose separation or monitoring. 7

• Ciprofloxacin bioavailability decreased by approximately 50% when coadministered with sevelamer. 7
• Mycophenolate mofetil: decreased mean MPA Cmax and AUC by 36% and 26%, respectively. 7
• Cases of increased TSH levels have been reported in patients coadministered sevelamer and levothyroxine. 7
• Reduction in concentrations of cyclosporine and tacrolimus may occur, potentially requiring dose increases in transplant patients. 7