What are the risks of hyperphosphatemia in a patient with Chronic Kidney Disease (CKD)?

From the Guidelines

Elevated phosphorus levels in chronic kidney disease (CKD) patients pose several serious health risks, including vascular calcification, secondary hyperparathyroidism, and accelerated kidney disease progression, emphasizing the need for careful management to mitigate these risks. The main dangers of hyperphosphatemia in CKD patients include:

• Vascular calcification, where calcium and phosphorus deposits form in blood vessels, leading to increased cardiovascular disease risk and mortality
• Secondary hyperparathyroidism, causing bone mineral disorders that result in bone pain, fractures, and skeletal deformities
• Acceleration of kidney disease progression
• Worsening of itching (pruritus)
• Calcium-phosphate deposits in soft tissues (calciphylaxis), which can lead to painful skin ulcers

Management of hyperphosphatemia in CKD patients typically involves:

• Dietary phosphorus restriction (limiting processed foods, dairy, and certain proteins)
• Phosphate binders (such as calcium acetate, sevelamer, lanthanum carbonate, or ferric citrate) taken with meals to prevent phosphorus absorption
• Adequate dialysis for end-stage patients Normal phosphorus levels should be maintained between 2.5-4.5 mg/dL for CKD patients, with specific targets depending on disease stage, as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline update 1. These interventions are crucial because phosphorus control becomes increasingly difficult as kidney function declines, since healthy kidneys normally excrete excess phosphorus to maintain balance.

From the FDA Drug Label

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD. 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).

The risks of hyperphosphatemia in a patient with Chronic Kidney Disease (CKD) include:

• Ectopic calcification due to high serum phosphorus precipitating serum calcium
• Secondary hyperparathyroidism The treatment of hyperphosphatemia in CKD patients can be achieved with phosphate binders such as sevelamer hydrochloride and calcium acetate, which can help lower serum phosphorus levels 2, 3.

From the Research

Risks of Hyperphosphatemia in CKD Patients

The risks associated with hyperphosphatemia in patients with Chronic Kidney Disease (CKD) are numerous and can have severe consequences on the patient's health. Some of the key risks include:

• Cardiovascular disease: Hyperphosphatemia has been linked to an increased risk of cardiovascular disease, including hypertension, vascular calcification, cardiac valvular calcification, atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis 4.
• Bone disease: Phosphate retention and hyperphosphatemia can contribute to bone disease, including abnormal bone mineralization and extra-osseous calcification 5, 6.
• Increased mortality: Hyperphosphatemia has been identified as an independent risk factor for mortality in dialysis patients, and even subtle increases in serum phosphate levels within the normal range can be associated with increased risk for death in predialysis and non-kidney disease populations 7.

Mechanisms of Hyperphosphatemia in CKD

The mechanisms by which hyperphosphatemia occurs in CKD patients are complex and involve multiple factors, including:

• Impaired phosphate excretion: As kidney function declines, the ability to excrete phosphate is impaired, leading to phosphate retention and hyperphosphatemia 5.
• Increased parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) levels: PTH and FGF-23 play important roles in phosphate homeostasis, and increased levels of these hormones can contribute to phosphate retention and hyperphosphatemia 5, 6.

Treatment Options for Hyperphosphatemia

Several treatment options are available for managing hyperphosphatemia in CKD patients, including:

• Dietary phosphate restriction: Restricting dietary phosphate intake can help reduce phosphate levels 5, 7.
• Phosphate binder therapy: Phosphate binders, such as calcium-based and non-calcium-based binders, can help reduce phosphate levels by binding to phosphate in the gut and preventing its absorption 6, 8, 7.
• Vitamin D supplementation: Vitamin D supplementation can help improve vitamin D deficiency and reduce PTH levels, but may worsen phosphate retention and increase FGF-23 levels 5.