What are the implications of hyperphosphatemia (elevated phosphorus level of 5.6)?

From the Guidelines

A phosphorus level of 5.6 mg/dL is mildly elevated and requires monitoring and possible intervention, with dietary phosphorus restriction as the first step, as suggested by the Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update 1.

Key Considerations

• The normal range for phosphorus is typically 2.5-4.5 mg/dL, and levels above this range may require intervention to prevent complications such as cardiovascular disease and bone disorders.
• Dietary phosphorus restriction is the first step in managing elevated phosphorus levels, with a focus on limiting intake of high-phosphorus foods like processed foods, dairy products, nuts, and cola beverages.
• Phosphate binders such as calcium acetate, sevelamer, or lanthanum carbonate may be prescribed if dietary changes are insufficient, and should be taken with meals to bind phosphorus in food and prevent absorption.

Treatment Approach

• The current evidence suggests that excess exposure to calcium may be harmful across all GFR categories of CKD, and phosphate-lowering treatment decisions should be individualized 1.
• The recommendation is to focus treatment on patients with hyperphosphatemia, rather than maintaining normal phosphate levels, and to avoid hypercalcemia in adult patients with CKD G3a to G5D 1.
• Regular monitoring of phosphorus, calcium, and parathyroid hormone levels is important to assess treatment effectiveness and prevent complications.

Important Findings

• High-quality evidence links high phosphate concentrations with mortality among patients with CKD stage G3a to G5 and transplant recipients 1.
• There is still a lack of data from clinical trials showing that therapeutic approaches to decreasing serum phosphate levels improve patient-centered outcomes.
• The current evidence suggests that prevention rather than treatment of hyperphosphatemia may be valuable in patients with CKD stage G3a to G5D, but future studies will need to address the potential value of hyperphosphatemia prevention in at-risk CKD populations 1.

From the FDA Drug Label

The ability of sevelamer hydrochloride to lower serum phosphorus in CKD patients on dialysis was demonstrated in six clinical trials: one double-blind placebo-controlled 2-week study (sevelamer hydrochloride N=24); two open-label uncontrolled 8-week studies (sevelamer hydrochloride N=220) and three active-controlled open-label studies with treatment durations of 8 to 52 weeks (sevelamer hydrochloride N=256). Eighty-four CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus >6 mg/dL) following a two-week phosphate binder washout period received sevelamer hydrochloride and active-control for eight weeks each in random order. Table 5: Mean Serum Phosphorus (mg/dL) at Baseline and Endpoint Sevelamer Hydrochloride Tablets (N=81) Active-Control (N=83) Baseline at End of Washout 8.4 8 Endpoint 6.4 5.9 Change from Baseline at Endpoint (95% Confidence Interval) -2* (-2.5, -1.5) -2.1* (-2.6, -1.7) Two hundred CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus >5. 5 mg/dL) following a two-week phosphate-binder washout period were randomized to receive sevelamer hydrochloride 800 mg tablets (N=99) or an active-control (N=101). Table 6: Mean Serum Phosphorus (mg/dL) and Ion Product at Baseline and Change from Baseline to End of Treatment Sevelamer Hydrochloride Tablets Active-Control (N=94) (N=98) Phosphorus Baseline 7.5 7.3 Change from Baseline at Endpoint -2.1 -1.8

For a patient with elevated phosphorus of 5.6, the expected outcome with sevelamer is a reduction in serum phosphorus levels.

• The mean reduction in serum phosphorus in clinical trials ranged from -1.6 to -2.1 mg/dL.
• The average daily dose of sevelamer hydrochloride used in these studies ranged from 4.9 to 6.5 g.
• It is essential to monitor serum phosphorus levels and adjust the dose of sevelamer hydrochloride as needed to achieve the desired level of phosphorus control 2.

From the Research

Elevated Phosphorus Levels

Elevated phosphorus levels, also known as hyperphosphatemia, can have serious health consequences, particularly in patients with chronic kidney disease (CKD) 3, 4, 5.

Health Consequences

• Hyperphosphatemia is correlated with an increased rate of mortality and morbidity due to cardiovascular diseases in CKD patients 3.
• If left untreated, hyperphosphatemia can result in secondary hyperparathyroidism, renal osteodystrophy, and metastatic calcification of blood vessels and soft tissue 5.
• Elevated phosphorus levels can also lead to an increased risk of cardiovascular diseases and mortality in patients undergoing dialysis 4.

Treatment Options

• Phosphate binders, such as lanthanum carbonate and sevelamer carbonate, can be used to manage hyperphosphatemia in CKD patients 3, 4, 6.
• Lanthanum carbonate has been shown to be more efficacious in lowering serum phosphate concentrations and effectively managing hyperphosphatemia compared to sevelamer carbonate 3.
• Other phosphate binders, including calcium carbonate, calcium acetate, and sevelamer hydrochloride, are also available, but their use may be limited by certain factors, such as gastric pH range and potential for calcium overload 5, 6.

Management of Hyperphosphatemia

• The treatment of hyperphosphatemia in patients with chronic renal failure includes dialysis, dietary phosphorus restrictions, phosphate-binding medications, and vitamin D analogs 5.
• Selection of phosphate binders should be based on patient characteristics, including serum phosphate, serum calcium, and intact parathyroid hormone concentrations, and patient tolerability 5, 6.