What are the treatment guidelines for patients with hypo or hyperphosphatemia, particularly those with chronic kidney disease or impaired renal function?

Management of Hypophosphatemia and Hyperphosphatemia

In patients with CKD stages 3-5D, treat hyperphosphatemia by lowering elevated phosphate levels toward the normal range using dietary restriction and phosphate binders, while avoiding treatment of normal phosphate levels with binders; for hypophosphatemia, use oral phosphate supplementation (0.5-1.0 g elemental phosphorus daily in divided doses) combined with calcitriol, reserving IV phosphate (0.16 mmol/kg at 1-3 mmol/h) only for life-threatening cases with serum phosphate <2.0 mg/dL. [@2,3@]12

Hyperphosphatemia Management

When to Treat

• Treat only when hyperphosphatemia is present, not to prevent it in patients with normal phosphate levels. The KDIGO 2017 guideline abandoned the previous recommendation to maintain normal phosphate levels in CKD stages 3a-4, after a trial showed phosphate binders in patients with normal phosphate increased coronary calcification without clinical benefit. [@2,3,4,6@]

• Base treatment decisions on trends of serial measurements of phosphate, calcium, and PTH together, not single laboratory values. These biomarkers interact significantly in predicting mortality and cardiovascular events. [@2,3,4,6@]

Target Ranges by CKD Stage

• CKD stages 3-4: Maintain serum phosphorus ≥2.7 mg/dL (0.87 mmol/L) and ≤4.6 mg/dL (1.48 mmol/L) 1

• CKD stage 5 and dialysis patients: Maintain serum phosphorus between 3.5-5.5 mg/dL (1.13-1.78 mmol/L) 13

Treatment Algorithm for Hyperphosphatemia

Step 1: Dietary Restriction

• Restrict dietary phosphorus to 800-1,000 mg/day when serum phosphorus exceeds 5.5 mg/dL in dialysis patients 3
• Focus patient education on avoiding processed foods containing inorganic phosphate additives, which have nearly 100% absorption compared to organic phosphates 3
• Monitor serum phosphorus monthly following dietary restriction 3

Step 2: Phosphate Binder Selection (when dietary restriction fails)

The choice depends on calcium and PTH levels:

• If calcium is normal AND PTH >150 pg/mL: Use either calcium-based binders (calcium acetate or carbonate, limiting elemental calcium to <1 g/day) OR non-calcium binders (sevelamer, lanthanum carbonate) 34

• If hypercalcemia present (corrected calcium >10.2 mg/dL): Use ONLY non-calcium binders (sevelamer or lanthanum carbonate) 3

• If low PTH (<150 pg/mL on 2 consecutive measurements): AVOID calcium-based binders entirely 3

Step 3: Dialysis Optimization

• Ensure adequate dialysis with target Kt/V of approximately 1.6, as inadequate dialysis worsens hyperphosphatemia and associated symptoms like pruritus 3

Phosphate Binder Dosing

• Sevelamer: Average effective dose ranges from 4.9-6.5 g daily (range 0.8-14.3 g), divided with meals, titrated every 2-4 weeks to achieve target phosphorus reduction of approximately 2 mg/dL 5

• Calcium-based binders: Average daily dose of 1.2-2.3 g elemental calcium in trials, but recommend limiting to <1 g elemental calcium to avoid positive calcium balance and vascular calcification 4

Critical Pitfall to Avoid

Do not use phosphate binders in CKD patients with normal baseline phosphate levels. This approach increases coronary calcification without improving outcomes and represents inappropriate preventive therapy. [@2,3,6@]

Hypophosphatemia Management

Diagnostic Approach

• Calculate fractional phosphate excretion first. If >15% in the presence of hypophosphatemia, renal phosphate wasting is confirmed 2

• Classify by serum calcium level:

  • High calcium = primary hyperparathyroidism
  • Low calcium = secondary hyperparathyroidism
  • Normal calcium = primary renal phosphate wasting 2

When to Treat

• Treat symptomatic patients OR those with chronic renal phosphate wasting regardless of symptoms 2

• Severe hypophosphatemia (<1.2 mg/dL) requires prompt treatment due to risk of rhabdomyolysis, cardiac arrhythmias, respiratory failure, and neurological complications 67

Treatment by Severity

Mild-Moderate Hypophosphatemia (Serum phosphate 1.2-2.5 mg/dL):

• Oral phosphate supplements: 0.5-1.0 g elemental phosphorus daily in divided doses 2
• Combine with calcitriol (20-30 ng/kg daily) or alfacalcidol (30-50 ng/kg daily) for renal phosphate wasting syndromes 1
• Take phosphate supplements 4-6 times daily initially, reducing to 3-4 times daily once alkaline phosphatase normalizes 1

Severe/Life-Threatening Hypophosphatemia (Serum phosphate <2.0 mg/dL):

• IV phosphate: 0.16 mmol/kg administered at 1-3 mmol/h until level reaches 2 mg/dL 2
• For renal failure patients, use slower infusion rate of 2.5-3.0 mg phosphate/kg body weight every 6-8 hours via central line, continuing until phosphate reaches 5.0-5.5 mg/dL 7
• The slower rate in renal patients allows full mineral equilibration and avoids hyperkalemia 7

Special Populations

Post-kidney transplant patients:

• Hypophosphatemia persists in 5% at 1 year post-transplant due to persistent hyperparathyroidism, immunosuppressive drugs, and reduced intestinal absorption 6
• Monitor closely and treat with oral phosphate plus calcitriol 6

Patients receiving ferric carboxymaltose (FCM):

• FCM causes hypophosphatemia in 47-75% of patients, with severe cases lasting up to 6 months 6
• Avoid FCM in patients with recurrent blood loss, malabsorptive disorders, or severe iron deficiency 6
• Switch to alternative IV iron formulations if repeat infusions needed 6

ICU patients on CRRT:

• 60-80% develop hypophosphatemia during continuous renal replacement therapy 6
• Monitor phosphate closely and supplement proactively 6

Monitoring During Treatment

• Check serum phosphorus monthly during treatment adjustments 3
• Monitor ionized calcium serially during IV phosphate repletion, as hypocalcemia occurs frequently but is usually asymptomatic 7
• For X-linked hypophosphataemia on burosumab, monitor fasting phosphate 7-11 days after injection during titration to avoid hyperphosphatemia, then before injections once stable 1