Aluminum (Al) is the most abundant metal and the third most prevalent element in the Earth’s crust, found ubiquitously in soil, water, and air. Although naturally present in the human body, it serves no known biological function. The body usually manages this constant, low-level exposure effectively, maintaining only trace amounts in the bloodstream. When blood aluminum levels rise significantly above the normal range, hyperaluminemia occurs, signifying a failure to control the total aluminum burden. This elevated state is a serious concern because the metal can accumulate in various organs, leading to toxic effects.
Impaired Kidney Function
The primary factor determining aluminum accumulation is the health of the renal system, as the kidneys eliminate most absorbed aluminum. Under normal circumstances, over 95% of the aluminum entering the bloodstream is filtered out and excreted in the urine. This efficient process prevents the small amount absorbed from building up to harmful levels.
In patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), this clearance mechanism fails. When the glomerular filtration rate (GFR) drops significantly, the ability to excrete aluminum is severely compromised. Even a normal daily intake of aluminum, which a healthy person manages easily, leads to the retention and slow accumulation of the metal in various body tissues.
The retained aluminum binds to plasma proteins, primarily transferrin, which deposits the metal in tissues with high turnover rates. Accumulation is pronounced in the bone, brain, and parathyroid glands. For patients with ESRD, the inability to clear aluminum turns small, unavoidable exposures into a cumulative toxic load, making them the most susceptible population for developing high blood aluminum levels.
Major Clinical Exposure Sources
While impaired kidney function is necessary for systemic accumulation, the most clinically significant hyperaluminemia cases link to high-dose, medically administered sources. These iatrogenic exposures bypass the gastrointestinal tract’s natural protective barrier or introduce large quantities directly into the body. Historically, a recognized source was contaminated dialysate fluid used during hemodialysis treatments.
If the water used to prepare the dialysate was not purified, high concentrations of aluminum could enter the patient’s bloodstream directly. Although modern purification standards have largely mitigated this risk, this contamination caused widespread toxicity outbreaks in the 1970s and 1980s.
Another major source in renal patients is the long-term use of aluminum-containing phosphate binders, such as aluminum hydroxide. These binders are taken orally to control hyperphosphatemia by binding phosphate in the gut. Although gastrointestinal absorption is usually low, the large, chronic doses administered can lead to significant absorption, especially combined with impaired renal clearance.
Additionally, long-term total parenteral nutrition (PN) solutions are a recognized source of high-level aluminum exposure, particularly for vulnerable populations like premature infants or patients with intestinal failure. Aluminum contamination in PN often originates from additives. Since these nutrients are delivered intravenously, the absorbed aluminum bypasses the gut’s natural barrier, leading to a high systemic load. Premature infants are especially at risk because their immature kidneys result in poor clearance capacity and rapid tissue accumulation.
Everyday Environmental Routes
For the general population with healthy kidneys, everyday exposure rarely results in clinically significant hyperaluminemia because the body efficiently excretes the small amount absorbed. The most common route is through the diet, where daily intake ranges from about 3.4 to 9 milligrams. Aluminum is naturally present in food and water, and its content can increase via food additives or by leaching from aluminum cookware when cooking acidic foods.
Specific over-the-counter medications represent another potential, though temporary, source of high-level oral exposure. High doses of aluminum-containing antacids can introduce several grams of aluminum per day into the gastrointestinal tract. While intestinal absorption remains low, the quantity ingested provides a significant exposure load.
Inhalation is a route of concern mainly for occupational exposure. Workers involved in welding, mining, or manufacturing aluminum products may inhale fine aluminum dust particles. This can lead to accumulation in the lungs and a higher systemic burden compared to the general population.
Cosmetics and personal care products, such as antiperspirants, also contain aluminum compounds, leading to minor dermal exposure. Studies indicate that the amount absorbed through the skin is minimal and does not contribute significantly to the total body burden in a person with normal kidney function. These environmental sources become problematic only when a person’s ability to excrete the metal is compromised.
Health Consequences and Management
When aluminum accumulates due to impaired clearance, it interferes with numerous biochemical processes, leading to distinct toxic syndromes. A primary target is the central nervous system, where neurotoxicity manifests as dialysis encephalopathy, characterized by speech disorders, cognitive decline, and seizures. Accumulation in the brain disrupts neurotransmitter function and causes direct cellular damage.
Bone tissue is another major site of accumulation, resulting in aluminum-related bone disease or osteomalacia. Aluminum deposits at the bone mineralization front directly inhibit calcification, leading to weak bones, severe pain, and increased fracture risk. Aluminum can also contribute to microcytic, hypochromic anemia by interfering with iron metabolism and hemoglobin synthesis.
Diagnosis of hyperaluminemia typically begins with measuring serum aluminum levels; concentrations exceeding 100 micrograms per liter often indicate toxicity. For a definitive diagnosis of aluminum-related bone disease, a bone biopsy is the standard, revealing aluminum deposits at the bone-forming surfaces. Management involves two main strategies: reducing the source of exposure and actively removing the accumulated metal.
Reducing exposure means switching patients to aluminum-free phosphate binders or ensuring the use of highly purified dialysate water. For treatment, chelation therapy is employed using deferoxamine (DFO), which acts as a chelating agent. DFO binds to free aluminum, creating a compound that can be effectively filtered and removed by the kidneys or through dialysis, lowering the total body burden.