Hyperphosphataemia

Background

Phosphorus is the sixth most abundant element in the human body. It is critical for bone mineralisation, cellular structure, genetic coding, and energy metabolism. Many organic and inorganic forms exist. The adult body contains approximately 1000g of phosphorus, of which 80-90% is in bone. An additional 10-14% is intracellular and the remaining 1% is extracellular.

Hyperphosphatemia is considered significant when levels are greater than 5 mg/dL in adults or 7 mg/dL in children or adolescents.

Pathophysiology

Phosphorus homeostasis is normally maintained through several mechanisms. Gastrointestinal (GI) absorption must be matched by renal excretion, and cellular release is balanced by uptake in other tissues. Hormonal control is provided mainly by parathyroid hormone.

Hyperphosphatemia occurs when the phosphorus load (from GI absorption, exogenous administration, or cellular release) exceeds renal excretion and tissue uptake.

GI absorption

Phosphorus is present in nearly all foods, and GI absorption of dietary forms is very efficient. With low dietary intake, 80-90% is absorbed. When intake is greater than 10 mg/kg daily, 70% is absorbed. Normal daily dietary intake varies from 800-1500 mg.

Absorption occurs mainly in the jejunum, although some absorption occurs throughout the intestinal tract. A small amount of phosphorus is secreted into the GI tract

Serum phosphorus levels

Serum phosphorus levels rise after a large meal. Antacids decrease absorption because calcium, aluminum, and magnesium bind phosphorus into insoluble complexes.

Renal excretion and reabsorption

To maintain homeostasis, renal phosphorus excretion normally matches the amount of daily GI absorption.

Hyperphosphataemia occurs most often in patients with renal insufficiency. Most patients with acute or chronic renal failure have hyperphosphataemia to some degree. To avoid hyperphosphataemia, patients with end-stage renal disease and a GFR <30 must restrict their intake of dietary phosphorus. If dietary restriction alone does not reduce serum phosphate levels into the normal range, oral phosphate binders should be added to reduce absorption.

Sequelae of hyperphosphatemia

Hyperphosphataemia causes hypocalcaemia by precipitating calcium, decreasing vitamin D production, and interfering with parathyroid hormone-mediated bone resorption. Signs and symptoms of acute hyperphosphataemia are due to the effects of hypocalcaemia.

Prolonged hyperphosphataemia promotes metastatic calcification, an abnormal deposition of calcium phosphate in previously healthy connective tissues such as cardiac valves and in solid organs such as muscles. The calcium-phosphate product predicts the risk of metastatic calcification.

Vascular walls become calcified and arteriosclerotic, leading to increased systolic blood pressure, widened pulse pressure, and subsequent left ventricular hypertrophy.

Hyperphosphataemia is an independent risk factor contributing to the increased incidence of aortic and mitral stenosis and other cardiovascular disease among dialysis-dependent patients.

Hyperphosphataemia-induced resistance to parathyroid hormone contributes to secondary hyperparathyroidism and renal osteodystrophy.

Prolonged hyperphosphatemia is an independent risk factor for cardiovascular disease in patients with renal failure.

Causes

Phosphorus balance between intracellular and extracellular compartments and between bone and other tissues may be influenced by many factors. The most common cause of hyperphosphataemia is decreased renal excretion due to renal insufficiency from any cause.

All marked elevations of phosphorus involve significant addition of phosphorus to the extracellular compartment, usually with some impairment of renal function.

Treatment

Most symptoms and sequelae are due to secondary hypocalcaemia. Initial care is aimed at management and correction of the hypocalcaemia and its sequelae. Endpoints of therapy include resolution of symptoms and a serum calcium level within the low reference range.

• A secondary goal is to decrease the incidence of sequelae, which requires reducing serum phosphate to nearly normal levels, less than 5.5 mg/dL, and maintaining the calcium phosphate product less than 60.
• The ultimate goal is resolution of the underlying disease state(s) responsible for the hyperphosphataemia.

Oral binders are given to decrease GI absorption of phosphorus and thereby assist in managing serum phosphate levels.

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