PRODUCT UPDATE
Aluminum in the Dialysis Patient Megan A. Tichy, RD*
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luminum-based phosphate binders remain in use, and other aluminum-containing products remain available (many over-the-counter) to persons with chronic kidney disease. It is important to be aware of the different methods of aluminum ingestion, manifestations of aluminum toxicity, and how to care for a patient when aluminum toxicity is discovered.
Aluminum Ingestion The Joint Expert Committee on Food Additives (JECFA) established a provisional tolerable weekly intake of aluminum to be 0 to 7 mg/kg body weight.1 In a female 67 inches tall weighing 135 pounds, the upper limit of aluminum intake would be 430 mg/wk or 61.4 mg/day. In persons with normal kidney function, absorbed aluminum is largely excreted. However, aluminum can be retained in persons with chronic kidney disease (CKD), especially those requiring dialysis. Aluminum binds to albumin and transferrin in the serum. As a result, it does not cross the dialyzer membrane and is not removed during dialysis.2 Sources of aluminum absorption in the body include food, water, environment, cosmetics, and medicines. Although aluminum may occur naturally in soil and plant foods, it is highest in certain processed foods (Table 1).3-5 Aluminum additives are present in processed cheese, grain products, nondairy creamers, baking powder, and salt derivatives. Most unprocessed foods contain less than 5 mg/kg aluminum.7 Herbs are the exception to this rule, containing large amounts of aluminum, but are generally consumed in very small
*Renal Dietitian, UCSF Mount Zion Dialysis. Address reprint requests to Megan A. Tichy, RD, 1675 Scott St., San Francisco, CA 94115. © 2003 by the National Kidney Foundation, Inc. 1532-8503/03/1303-0015$30.00/0 doi:10.1053/jren.S1051-2276(03)00065-7
Journal of Renal Nutrition, Vol 13, No 3 ( July), 2003: p E1
Table 1. Estimated Aluminum Contents in a Variety of Foods
Food Baking powder Thyme Oregano Bay leaf Cornbread Cheese, processed Salt with aluminum derivatives Tortilla, flour Cheese, natural Bran, wheat
Aluminum Concentration (mg/100g) 2300.00 75.00 60.00 43.60 40.00 29.70 16.60 12.90 1.57 1.28
Data from Soni. et al, 2000; Gregar, 1992.
amounts. Cooking or storage in aluminum foods can increase the aluminum content in foods (Table 2).5 Drinking water contributes a minimal amount of aluminum to the total daily intake (3%).5 Aluminum salts are frequently used to remove turbidity and color during water purification. Water rich in aluminum may end up in dialysate. This aluminum can cross the dialyzer membrane and enter into a person’s blood.6 The risk of dialysate contamination is decreased in the U.S since the Association for the Advancement of Medical Instrumentation (AAMI) set a limit for aluminum in diluted dialysate. Water used in dialysis is generally treated with reverse osmosis and deionization. Aluminum is inhaled through the air and consumed via many plant products. Aluminum occurs naturally on 8% of the earth’s surface.4 The concentration of aluminum in the soil and in the air is known to increase near metal processing plants. The metallic ash emitted by such a plant is a source of aluminum deposition in the environment. As a result, waterways and plants located near metal processing may be richer in aluminum.5 Over the counter antacids, antiflatulent, antidiarE1
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MEGAN A. TICHY
Table 2. Affect of Cooking With Aluminum Pots and Pans
Food
Uncooked (ppm wet wt)
Cooked With Aluminum Pots and Pans (ppm wet wt)
0.13 0.13 0.10 0.47
7.10 3.60 1.60 1.00
Apple sauce Cabbage Eggs Chicken
Data from Soni et al, 2001.
rheal, antiulcerative, and buffered aspirin medications contain aluminum (Table 3) and are readily available to the dialysis population. When these medications are used several times daily for an extended time, the amount of absorbed aluminum can be significant. The ingestion of citrate salts (eg, Scholl’s solution, Alka-Seltzer) can markedly increase intestinal absorption of aluminum.7
Aluminum Toxicity Aluminum toxicity manifests itself predominantly in the bones, brain, and heart of dialysis patients. It has been suggested that osteoporosis may lead to bone demineralization and transfer of aluminum to other organs.4
Osteomalacia and adynamic bone disease can result from increased aluminum absorption.8 The aluminum crystals form at the site where calcium is laid in the bone matrix. As a result, the process of bone mineralization is disturbed. Aluminum directly inhibits the bone-building osteoblasts leading to decreased bone turnover. Neurotoxic effects from aluminum include memory loss, impaired coordination, tremor, loss of curiosity, ataxia, and jerking movements. Hemodialysis patients with high serum aluminum levels have also been observed to have a decrease in visual memory.4 The term “dialysis encephalopathy” is commonly used to describe speech disorder, dementia, and convulsions in patients exposed to large amounts of aluminum via dialysate.5 Elevated levels of aluminum have been noted in patients with Alzheimer’s disease. However, there are some studies supporting that the aluminum accumulation in the brain is not in the regions that are susceptible to neuropathologic changes.9 Further research is needed to determine whether it is a consequence that aluminum is elevated in people with Alzheimer’s disease or if aluminum is a cause of it. Cardiac hypertrophy in dialysis patients is correlated with aluminum deposits in the heart. In addition, aluminum is thought to accumulate in
Table 3. Over the Counter Aluminum-Containing Drugs Drug Class Antacid
Aluminum Salts Used Aluminum hydroxide Dihydroxyaluminum acetate Aluminum oxide
Internal analgesics (buffered aspirins)
Bismuth aluminate magaldrate Dihydroxyaluminum aminoacetate Dihydroxyaluminum sodium carbonate Aluminum hydroxide
Antidiarrheals
Aluminum glycinate Kaolin
Anti-ulcerative
Aluminum magnesium silicate Aluminum sucrose sulfate
Brand Names
Aluminum Content/ Dose (mg)
Alurex, Di-Gel, Gelusil, Maalox, Mylanta Aluscop Magnesia and Alumina Oral Suspension, Nutramag Noralac Riopan, Riopan Plus Robalate, Tralmag
35-208
Rolaids
63
Ascriptin, Arthritis Pain Formula, Pabrin Bufferin Extra Strength Amogel, Kaopectate, Parepectolin, Pargel Pabisol with Paregoric Carafate
9-52
45-72 41 55 51-61 100
35,717 120-1,450 36 207
Alurex (Rexall, Boca Raton, FL); Di-Gel (Schering-Plough, Liberty Corner, NJ); Gelusil (Pfizer Canada, Inc., Toronto, ON); Maalox (Novartis, Summit, NJ); Mylanta (Johnson & Johnson–Merck, Fort Washington, PA); Noralac (Vortech, Dearborn, MI); Riopan (Whitehall-Robins, Madison, NJ); Robalate (Wyeth-Ayerst, Philadelphia, PA); Rolaids (Warner Lambert, Morris Plains, NJ); Ascriptin (Rhone-Poulenc Rorer, Bombay, India); Arthritis Pain Formula (MedTech Laboratories, Jackson, WY); Bufferin Extra Strength (Astra Pharmaceuticals, North Ryde, Australia); Amogel (Vortech, Dearborn, MI); Kaopectate (Rhone-Poulenc Rorer); Carafate (Aventis, Kansas City, MO).
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PRODUCT UPDATE
the myocardium and lead to cardiomyopathy. Arrhythmia and sudden death in hemodialysis patients may result.4
Treatment of Aluminum Toxicity The most important method of treating aluminum toxicity is to prevent further exposure to aluminum. It is important to remember that dialysis patients are at a greater risk than the general population to experience side effects from aluminum. Desferrioxamine (DFO) can be used as a chelating agent to promote aluminum mobilization from tissues into the serum where it can be dialyzed out of the body. Doses ⬍5 mg/kg are shown to be effective. Higher doses have been associated with cerebral, auditory, and visual side effects.10 In addition, systemic mucormycosis (a fungal infection) developed in a high fraction of patients treated with DFO at higher doses.11 Aluminum is an important element to consider in the care of a dialysis patient. Clearly, more research is needed to establish a better understanding of some of the correlations with aluminum in the body. For now, I hope that as clinicians we can ask enough questions of our patients to help identify causes of aluminum toxicity.
References 1. Food Additives Council, International: Memorandum dated May 29, 2002, from the Dockets Management, 2002 2. Food and Drug Administration (FDA): Code of federal regulations, Title 21, Vol 5, Part 331. Antacid products for over-the-counter (OTC) human use. 2002 3. Greger JL: Dietary and other sources of aluminum, in Chadwick DJ, Whelan J (eds): Aluminum in Biology and Medicine. Ciba Foundation Symposium No. 169. New York, NY, Wiley, 1992, pp 2649 4. Nayak P: Review aluminum: Impacts and disease. Environmental Research Section A 89:101-115, 2002 5. Soni MG, White SM, Flamm WG, Burdock GA: Safety evaluation of dietary aluminum. Regul Toxicol Pharmacol 33: 66-79, 2001 6. De Wolf FA, Berend K, Van der Voet GB: Subacute fatal aluminum poisoning in dialyzed patients: post-mortem toxicological findings. Forensic Sci Int 128:41-43, 2002 7. Brunier GM: Calcium/phosphate imbalances, aluminum toxicity, and renal osteodystrophy. ANNA J 21:171-177, 1994 8. Malluche HH: Aluminum and bone disease in chronic renal failure. Nephrol Dial Transplant 17(suppl 2):21-24, 2002 9. Yves C: Oxidative stress and Alzheimer disease. Am J Clin Nutr 71:621S-629S, 2000 10. Cannata-Andia JB, Fernandez-Martin JL: The clinical impact of aluminum overload in renal failure. Nephrol Dial Transplant 17(suppl 2):9-12, 2002 11. Van Cutsem J, Boelaert JR: Effects of deferoxamine, feroxamine and iron on experimental mucormycosis (zygomycosis). Kidney Int 36:1061-1068, 1989