What are the causes and treatments of Hyperphosphatemia (elevated phosphate levels)?

From the Guidelines

Hyperphosphatemia should be treated with dietary phosphate restriction and phosphate binders, with a focus on individualized treatment decisions, as recommended by the Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update 1.

Treatment Approach

The treatment of hyperphosphatemia involves addressing the underlying cause, restricting dietary phosphate intake, and using phosphate binders.

• Patients should limit dietary phosphate intake to 800-1000 mg/day by reducing consumption of processed foods, dairy products, nuts, and cola beverages.
• Phosphate binders, such as calcium-based agents like calcium carbonate or calcium acetate, can be used to reduce phosphate levels.
• For patients with hypercalcemia or significant vascular calcification, non-calcium binders, such as sevelamer, lanthanum carbonate, or ferric citrate, are preferred.

Monitoring and Adjustments

Regular monitoring of serum phosphate, calcium, and parathyroid hormone levels is essential to guide therapy adjustments.

• Treatment approaches should be based on serial assessments of these variables taken together, as therapeutic maneuvers aimed at improving one variable often have unintended effects on others.
• The current evidence suggests that excess exposure to calcium may be harmful across all GFR categories of CKD, prompting the recommendation to avoid inappropriate calcium loading in adults whenever possible 1.

Individualized Treatment Decisions

Treatment decisions should be individualized, taking into account the patient's underlying condition, phosphate levels, and other biochemical variables.

• The recommendation is to treat patients with PTH values that are progressively increasing or persistently above the upper limit of normal and not to base treatment on a single elevated value 1.
• Future research should address the gaps in the knowledge base for treatment of CKD–MBD, including the comparison of calcium-containing and calcium-free phosphate binders and the effect of dietary phosphate intake on phosphate sources 1.

From the FDA Drug Label

Calcium acetate capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure. Patients with ESRD retain phosphorus and can develop hyperphosphatemia. Calcium acetate, when taken with meals, combines with dietary phosphate to form an insoluble calcium phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

Hyperphosphatemia Treatment: Calcium acetate is used to control hyperphosphatemia in end-stage renal failure. It works by combining with dietary phosphate to form an insoluble complex that is excreted in the feces, resulting in decreased serum phosphorus concentration.

• The studies demonstrate the efficacy of calcium acetate in decreasing serum phosphorus levels in patients with end-stage renal disease 2 2.
• There was a 30% decrease in serum phosphorus levels during the 12-week study period (p<0.01) and a 19% decrease after 2 weeks of treatment with calcium acetate (p<0.01).

From the Research

Hyperphosphatemia Management

• Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) that requires management to prevent cardiovascular mortality and other complications 3, 4, 5.
• Phosphate binders are the mainstay pharmacologic treatment to lower phosphorus levels in patients with CKD, with several classes available, including calcium-based, sevelamer, and lanthanum carbonate 4, 6, 7.

Phosphate Binders Comparison

• Sevelamer and lanthanum carbonate have been compared to calcium-based binders in several studies, with sevelamer showing a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared to calcium-based binders 3.
• Lanthanum carbonate has been shown to be a potent and selective phosphate binder that retains high affinity for phosphate over a wide pH range, does not bind bile acids or contribute to metabolic acidosis, and has the potential to reduce pill burden and increase patient compliance compared to other phosphate binders 4.
• Sevelamer carbonate has been shown to have favorable effects on anti-inflammatory and vascular calcification biomarkers compared to calcium acetate treatment in patients with CKD stages 3 and 4 with normal phosphorous values 5.

Treatment Considerations

• The choice of phosphate binder should be individualized based on patient characteristics, such as risk of metabolic acidosis, and treatment goals, such as reducing pill burden and improving patient compliance 6, 7.
• Clinical trials have not definitively demonstrated the superiority of any class of phosphate binders over another with regard to clinical outcomes, leading to uncertainty regarding the use and best choice of phosphate binders for patients with CKD or kidney failure 7.
• The use of phosphate binders contributes substantially to patients' pill burden and out-of-pocket costs, and many have side effects, highlighting the need for careful consideration of treatment options 7.