What happens to phosphorus levels in cases of Chronic Kidney Disease (CKD)?

From the Guidelines

In chronic kidney disease (CKD), phosphorus levels in the blood typically increase due to the kidneys' decreased ability to filter and excrete excess phosphorus, leading to hyperphosphatemia, which can cause secondary hyperparathyroidism, bone disease, and vascular calcification. This condition occurs because damaged kidneys cannot remove phosphorus efficiently through urine, and as kidney function declines, phosphorus accumulates in the bloodstream. The body attempts to compensate by increasing parathyroid hormone (PTH) production, which pulls calcium from bones to balance the high phosphorus levels, resulting in weakened bones over time.

Management of Hyperphosphatemia in CKD

Management typically involves:

• Dietary phosphorus restriction (limiting high-phosphorus foods like dairy, processed foods, and certain proteins)
• Phosphate binders (such as sevelamer, lanthanum carbonate, or ferric citrate) taken with meals to prevent phosphorus absorption
• In some cases, vitamin D analogs to help regulate calcium-phosphorus balance
• Dialysis also removes some phosphorus but is usually insufficient alone

According to the most recent guidelines, phosphate-lowering therapies may only be indicated in the event of progressive or persistent hyperphosphatemia and not for prevention 1. The current evidence suggests that excess exposure to calcium may be harmful across all GFR categories of CKD, and calcium-free phosphate-binding agents may be preferred over calcium-based agents for treatment of hyperphosphatemia 1.

Key Considerations

• Maintaining phosphorus control is critical as hyperphosphatemia contributes to increased cardiovascular risk and mortality in CKD patients
• Not all phosphate binders are interchangeable, and the choice of phosphate binder should be individualized based on the patient's specific needs and medical history
• The potential harm of liberal calcium exposure in normophosphatemic adults with CKD stage G3b or G4 should be considered when selecting a phosphate binder 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: 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) 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

In cases of Chronic Kidney Disease (CKD), the phosphorus levels in the blood increase. The use of sevelamer hydrochloride has been shown to lower serum phosphorus levels in CKD patients on dialysis.

• The mean serum phosphorus levels decreased by about 2 mg/dL in patients treated with sevelamer hydrochloride.
• The decrease in phosphorus levels was similar to that of the active-control.
• The median response was a reduction of about 2 mg/dL in both groups.
• About 50% of subjects had reductions in phosphorus levels between 1 and 3 mg/dL 2.

From the Research

Phosphorus in Chronic Kidney Disease

• In cases of chronic kidney disease (CKD), hyperphosphatemia contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk 3.
• The management of hyperphosphatemia in CKD patients involves dietary phosphorus restriction and phosphate binding agents, such as calcium acetate or sevelamer carbonate 3, 4.
• Treatment with calcium acetate has been shown to reduce serum phosphorus concentrations in pre-dialysis patients with CKD 3.
• Phosphate binders, such as sevelamer carbonate, can also reduce serum phosphate, calcium phosphate, and FGF-23 levels in patients with CKD stages 3 and 4 4.
• Maintaining plasma phosphorus concentrations within target ranges is recommended to improve survival time and reduce clinical manifestations of hyperphosphatemia and secondary hyperparathyroidism in CKD patients 5.

Biochemical Markers

• Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and alkaline phosphatase are commonly monitored in CKD patients to assess bone mineral metabolism 3, 6, 7.
• The calcium-phosphorus product is also an important marker, as elevated levels can increase the risk of cardiovascular mortality 6, 7.
• FGF-23 is a key regulator of plasma phosphorus concentration and has been implicated in the pathophysiology of secondary renal hyperparathyroidism 5.

Treatment Strategies

• Phosphate binders, such as calcium acetate and sevelamer carbonate, are commonly used to control serum phosphorus levels in CKD patients 3, 4.
• Vitamin D therapy, including calcitriol and paricalcitol, is also used to manage secondary hyperparathyroidism in CKD patients 6, 7.
• Dietary phosphorus restriction is an important aspect of managing hyperphosphatemia in CKD patients 5, 7.