Medical Management of the Dialysis Patient: Hyperphosphatemia

Does this patient have hyperphosphatemia?

Signs and symptoms

• Typically detected by routine laboratory tests

• Symptoms may include pruritus, bone or joint pain

• Signs may include radiographic evidence of vascular calcification, eye deposition leading to red eye or conjunctivitis, and calciphylaxis

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• Values may vary depending on time of day (circadian variation), prandial status, relationship to timing of dialysis, hemolysis of specimen, type of blood sample (serum vs. plasma)

• Controversies re appropriate level exist, with Kidney Disease Outcomes Quality Initiative recommending a range of 3-5 mg/dl and Kidney Disease: Improving Global Outcomes recommending levels to be maintained in the normal range

What tests to perform?

Lab Testing

• Should include serum phosphate, calcium, PTH, and indicators of dialysis adequacy (Kt/V or URR)

• Elevated phosphate levels may be accompanied by hypocalcemia and secondary hyperparathyroidism and are indicators of severity of global mineral metabolism abnormalities

• Serum phosphate levels are typically checked routinely in outpatient dialysis units on at least monthly basis

• If treatments are actively being titrated up or down, then more frequent serum phosphate checks may be needed

• If dialysis adequacy is suboptimal, it may worsen hyperphosphatemia and thus adequacy should be monitored and maximized

• Medications, compliance with prescriptions, time of intake of binders in relation to meals, and diet should be reviewed along with lab work

Imaging

• If dialysis adequacy is suboptimal, then imaging studies to assess vascular access patency may be needed

Biopsy

• If painful non-healing ulcers are discovered and the diagnosis of calciphylaxis is being entertained, a skin biopsy may provide the definitive diagnosis, especially when other skin lesions are also in the differential diagnosis (e.g. Coumadin-induced skin necrosis)

Overall Interpretation of test results

• Trends in serum phosphate values are more useful than single measurements

Controversies in diagnostic testing

• Kidney Disease Outcomes Quality Initiative recommends checking serum phosphate levels on monthly basis

• Kidney Disease: Improving Global Outcomes recommends checking serum phosphate levels 1-3 months

How should patients with hyperphosphatemia be managed?

Dietary restriction

• Usual American diet contains ~800 to 2000 mg of phosphorus/day

• Major sources of dietary phosphorus are

  Meat

  Fish

  Dairy

  Grains

  Vegetables

  Soft drinks

• Dietary counseling is a crucial component of management

• Specific attention needs to be paid to detailed evaluation of components of dietary phosphorus intake:

  animal vs vegetable protein

  processed food with additives rich in highly bioavailable phosphorus

• Counseling for dietary phosphorus restriction must be balanced with risk for protein malnutrition

• Counseling to avoid foods with additives may decrease serum phosphate levels

• Vegetarian protein contains phosphorus that is less bioavailable than animal protein and may be the preferred source of protein

Phosphate binders

• Because dietary restriction is limited by dietary protein needs, diminishing residual renal function and urinary phosphate excretion, and limited dialytic phosphate removal, additional means of preventing phosphate accumulation are needed

• Phosphate binders fill this gap; use increases with increased dialysis vintage

• Poor compliance with binder therapy may be a barrier to control

• Poor compliance with phosphate binders may be multi-factorial

  Average dialysis patient is on numerous medications

  Compliance with three times a day drugs is lower than with once daily medications

  Pill burden with certain classes of phosphorus binders is large

  Gastrointestinal side effects/lack of palatability may limit compliance

• Education about proper intake of medications in relation to food is important

• Education about importance of therapy may improve compliance

• Largest dose of binder should coincide with largest meal of the day

• Administered three times a day with meals

• Several classes exist

  Aluminum-based phosphate binders

  ▪ Trap phosphate ions in the blood and form unabsorbable aluminum phosphate precipitates in the gut

  ▪ Useful for short-term therapy

  ▪ Toxicities (cognitive, bone, heme) prevent long-term use

  Calcium-based phosphate binders

  Calcium carbonate

  Calcium acetate

  Both are effective, inexpensive but use has been curtailed by some due to concerns re hypercalcemia (especially when used in conjunction with active vitamin D) and contribution to vascular calcification (although still controversial and data on hard clinical outcomes lacking)

  Recent meta-analyses suggest that calcium carbonate and calcium acetate have similar efficacy in lowering phosphate levels and similar tolerability

  Non-calcium based phosphate binders

  Sevelamer hydrochloride

  ▪ Metabolic acidosis

  ▪ Large pill burden

  ▪ Cost

  Severlamer carbonate

  ▪ Developed to address concern of metabolic acidosis with sevelamer hydrochloride

  Lanthanum carbonate

  ▪ Potent, less pills needed to accomplish control of serum phosphate

  ▪ Long-term data on safety available for 9 years of follow-up

  ▪ Gastrointestinal (GI) side effects limiting (tolerability may be improved when starting a lowest dose and slowly titrating up)

  ▪ Cost

  Magnesium-based phosphate binders

  Iron-based phosphate binders: Effectively lowers phosphate; Beneficial effects on iron stores and anemia management

• Intensity/adequacy of dialysis (Table I)

  Serum phosphate rapidly cleared within first 2 hours of hemodialysis

  Levels rebound 3-4 hours post-treatment

  Total amount removed by one hemodialysis treatment on average are 500-1000 mg

• Adjustment of other medications

  Active vitamin D

  ▪ Increases dietary phosphorus absorption –> binder dose may need to be titrated up

  ▪ Increases calcium absorption –> risk of hypercalcemia with calcium-based phosphate binders may increase