How is hyperphosphatemia managed in patients with Chronic Kidney Disease (CKD)?

Management of Hyperphosphatemia in Chronic Kidney Disease

In patients with CKD G3a-G5D, initiate phosphate-lowering treatment only for progressively or persistently elevated serum phosphate—not for prevention—starting with dietary phosphate restriction (800-1,000 mg/day), followed by phosphate binders when dietary measures fail, with calcium-based binders restricted in dose and avoided entirely in patients with vascular calcification, hypercalcemia, or suppressed PTH. 1

When to Initiate Treatment

Treatment decisions should be based on serial assessments of phosphate, calcium, and PTH levels considered together, not isolated single values. 1, 2 The 2017 KDIGO guidelines represent a critical shift from the 2009 recommendations: normophosphatemia is no longer an indication to start phosphate-lowering treatments. 1, 3 This change reflects evidence that preventing hyperphosphatemia may cause more harm than benefit, particularly with calcium-based binders in patients with normal phosphate levels. 1

• Initiate treatment only when phosphate levels are progressively rising or persistently elevated, not for isolated elevated values 1, 2
• For CKD G3a-G4, consider treatment when serum phosphorus exceeds 4.6 mg/dL despite dietary restriction 3, 4
• For CKD G5D (dialysis), target serum phosphorus between 3.5-5.5 mg/dL 3, 4

Step 1: Dietary Phosphate Restriction (First-Line)

Limit dietary phosphate intake to 800-1,000 mg/day as the initial approach for all patients with elevated phosphorus. 3, 4 This should be adjusted based on protein needs to maintain adequate protein intake of 1-1.2 g/kg/day. 4

Phosphate Source Matters

The bioavailability of phosphorus varies dramatically by source, which should guide dietary recommendations: 1, 2, 3

• Animal-based phosphate: 40-60% absorbed 1, 2, 3
• Plant-based phosphate (with phytates): 20-50% absorbed 1, 2, 3
• Inorganic phosphate in food additives: Much higher absorption, often >90% 1, 2, 3

Avoid phosphate additives in processed foods, which can double phosphorus intake compared to unprocessed foods. 4 Choose proteins with lower phosphorus-to-protein ratios (12-16 mg phosphorus per gram protein). 4

Critical Caveat on Dietary Restriction Alone

Dietary phosphate restriction alone is usually insufficient in most CKD patients and requires the addition of binders. 3 Achieving <1,000 mg phosphorus while maintaining adequate protein (1-1.2 g/kg/day) is extremely difficult—expect phosphorus intake of 778-1,444 mg at this protein level. 4

Step 2: Phosphate Binders (When Dietary Measures Fail)

For CKD G3a-G4 (Non-Dialysis)

Start with calcium-based phosphate binders (calcium acetate or calcium carbonate) when serum phosphorus exceeds 4.6 mg/dL despite dietary restriction. 3, 4 However, the dose must be strictly limited:

• Limit elemental calcium from binders to ≤1,500 mg/day 1, 3, 4
• Total calcium intake (including dietary) should not exceed 2,000 mg/day 3, 4

This represents a major shift from earlier practice. Evidence now shows that excess calcium exposure may be harmful across all GFR categories of CKD, potentially causing positive calcium balance and progression of vascular calcification even in normophosphatemic patients. 1

For CKD G5D (Dialysis Patients)

Either calcium-based binders or non-calcium binders can be used as primary therapy, but non-calcium binders should be strongly preferred in specific high-risk situations. 3, 4

Avoid calcium-based binders entirely if: 3, 4

• Severe vascular or soft-tissue calcifications are present
• Hypercalcemia exists (corrected calcium >10.2 mg/dL)
• PTH is suppressed (<150 pg/mL on 2 consecutive measurements)

The choice of binder should consider CKD stage, presence of other CKD-MBD components, concomitant therapies, and side effect profile. 1, 2 Not all phosphate binders are interchangeable. 1

Aluminum-Containing Binders

Avoid long-term use of aluminum-containing phosphate binders to prevent aluminum intoxication. 1, 2 For severe hyperphosphatemia (>7.0 mg/dL), aluminum-based binders may be considered for short-term use only (4 weeks maximum, one course only), then switch to other binders. 3, 4

Non-Calcium Binders

Sevelamer (both hydrochloride and carbonate forms) effectively lowers serum phosphorus by approximately 2 mg/dL in dialysis patients. 5 Average doses range from 4.9-6.5 g/day. 5 The main adverse events are gastrointestinal effects. 6

Important drug interactions with sevelamer: 5

• Decreases ciprofloxacin bioavailability by ~50%
• Decreases mycophenolate mofetil exposure (MPA Cmax by 36%, AUC by 26%)
• May increase TSH levels when coadministered with levothyroxine
• May reduce cyclosporine and tacrolimus concentrations in transplant patients

Step 3: Combination Therapy for Persistent Hyperphosphatemia

If hyperphosphatemia persists (>5.5 mg/dL) despite monotherapy, combine calcium-based and non-calcium-based binders. 3 This approach may yield additive benefits. 7

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, 4

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

Monitoring and Target Adjustments

Maintain corrected total serum calcium in the normal range, preferably 8.4-9.5 mg/dL (lower end of normal) for dialysis patients. 3, 4 Avoid hypercalcemia in adult patients with CKD G3a-G5D. 1, 2

Maintain Ca × P product <55 mg²/dL². 4

If corrected calcium exceeds 10.2 mg/dL, reduce or discontinue calcium-based binders and switch to non-calcium 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. 1, 2 Correcting hyperphosphatemia is a critical first step before addressing PTH directly. 1

For patients with CKD G5D, maintain intact PTH levels in the range of approximately 2-9 times the upper normal limit for the assay. 1, 2 For those requiring PTH-lowering therapy, use calcimimetics, calcitriol, or vitamin D analogs, or a combination. 1

Special Populations

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

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. 3 Excess calcium exposure from calcium-based binders may contribute to cardiovascular calcification across all stages of CKD. 1, 3

Patients with vascular or valvular calcification should be considered at highest cardiovascular risk, and this information should guide management decisions—specifically favoring non-calcium binders. 1, 2

Overly aggressive PTH suppression can lead to adynamic bone disease. 2 Normal or low PTH levels in ESRD may indicate adynamic bone disease, which is also problematic. 2

Dietary phosphate restriction alone is insufficient and can lead to maladaptive increases in NaPi2b expression, potentially increasing phosphate absorption efficiency. 8, 9 This is why phosphate binders are nearly always necessary.