Pediatric Nephrology

, Volume 6, Issue 4, pp 383–393 | Cite as

Aluminum toxicity in childhood

  • Aileen Sedman
Invited Review


Aluminum intoxication is an iatrogenic disease caused by the use of aluminum compounds for phosphate binding and by the contamination of parenteral fluids. Although organ aluminum deposition was noted as early as 1880 and toxicity was documented in the 1960s, the inability to accurately measure serum and tissue aluminum prevented delineation of its toxic effects until the 1970s. Aluminum toxicity has now been conclusively shown to cause encephalopathy, metabolic bone disease, and microcytic anemia.

Key words

Aluminum Childhood renal failure Encephalopathy Osteomalacia Microcytic anemia Aluminum-containing antacids 


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  1. 1.
    deBroe MD, Coburn JW (1990) Aluminum and renal failure. Dev Nephrol 26:1–4Google Scholar
  2. 2.
    Smith EE (1928) Aluminum compounds in food. Hoeber, New York, pp 222–229, 248, 325–327Google Scholar
  3. 3.
    Kerr DNS, Ward MK (1986) The history of aluminum related disease. In: Taylor A (ed) Aluminum and other trace elements in renal disease. Baillière Tindall, LondonGoogle Scholar
  4. 4.
    McLaughlin AIG, Kazantzis G, King E, Teare D, Porter RJ, Owen R (1962) Pulmonary fibrosis and encephalopathy associated with the inhalation of aluminum dust. Br J Ind Med 19:253Google Scholar
  5. 5.
    Kerr DNS, Walls J, Ellis H, Simpson W, Uldall PR, Ward MK (1969) Bone disease in patients undergoing regular hemodialysis. J Bone Joint Surg [Br] 51B:578Google Scholar
  6. 6.
    Berlyne GM, Ben Ari J, Pest D, Weinberger J, Stern M, Gilmore GR, Levine R (1970) Hyperaluminemia from Al resins in renal failure. Lancet II: 494Google Scholar
  7. 7.
    Alfrey AC, Mishell JM, Burks J (1972) Syndrome of dyspraxia and multi-focal seizures associated with chronic hemodialysis. Trans ASAIO 18:257Google Scholar
  8. 8.
    Alfrey AC, Legendre GR, Kaehny WD (1976) The dialysis encephalopathy syndrome. Possible aluminum intoxication. N Engl J Med 294:184–188Google Scholar
  9. 9.
    Baluarte HJ, Gruskin AB, Hiner L, Foley CM, Grover WD (1977) Encephalopathy in children with chronic renal failure. Proc Clin Dial Transplant Forum 7:95–98Google Scholar
  10. 10.
    Ward MK, Feest TG, Ellis HA, Parkinson IS, Kerr DNS, Herrington J, Goode GL (1978) Osteomalacia dialysis osteodystrophy: evidence for a water-borne agent, probably aluminum. Lancet I:841–845Google Scholar
  11. 11.
    Ackrill P, Ralston AJ, Day JP, Hodge KC (1980) Successful removal of aluminum from a patient with dialysis encephalopathy. Lancet II:692Google Scholar
  12. 12.
    Short AIK, Winney RJ, Robson JS (1980) Reversible microcytic hypochromic anaemia in dialysis patients due to aluminum intoxication. Proc Eur Dial Transplant Assoc 17:226Google Scholar
  13. 13.
    Andreoli SP, Bergstein JM, Sherrard DJ (1984) Aluminum intoxication from aluminum-containing phosphate binders in children with azotemia not undergoing dialysis. N Engl J Med 310:1079–1084Google Scholar
  14. 14.
    Griswold WR, Reznik V, Mendoza SA, Trauner D, Alfrey AC (1983) Accumulation of aluminum in a nondialyzed uremic child receiving aluminum hydroxide. Pediatrics 71:56–58Google Scholar
  15. 15.
    Sedman AB, Miller NL, Warady BA, Lum GA, Alfrey AC (1984) Aluminum loading in children with chronic renal failure. Kidney Int 26:201–204Google Scholar
  16. 16.
    Salusky IB, Coburn JW, Paunier L, Sherrard DJ, Fine RN (1984) Role of aluminum hydroxide in raising serum aluminum levels in children undergoing continuous ambulatory peritoneal dialysis. J Pediatr 105:717–720Google Scholar
  17. 17.
    Andreoli SP, Dunn D, DeMeyer W, Sherrard DJ, Bergstein JM (1985) Intraperitoneal deferoxamine therapy for aluminum intoxication in a child undergoing continuous ambulatory peritoneal dialysis. J Pediatr 107:760–763Google Scholar
  18. 18.
    Sedman AB, Klein GL, Merritt RJ, Miller NL, Weber KO, Gill WL, Anand H, Alfrey AC (1985) Evidence of aluminum loading in infants receiving intravenous therapy. N Engl J Med 312:1337–1343Google Scholar
  19. 19.
    Slanina P French W, Ekstrom LG, Loof L, Slorach S, Cedergren A (1985) Dietary citric acid enhances absorption of aluminum in antacids. Clin Chem 32:539–541Google Scholar
  20. 20.
    Slatopolsky E, Weerts C, Lopez-Hilker S (1986) Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 315:157–161Google Scholar
  21. 21.
    Salusky IB, Coburn JW, Foley J, Fine RN (1986) Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis. J Pediatr 108:767–770Google Scholar
  22. 22.
    Sedman A, Bozynski M, Karra M, Chan J (1989) Risk factors for aluminum (Al) toxicity in childhood. Pediatr Nephrol 3:C134Google Scholar
  23. 23.
    Federal Register (1990) Vol 55, no. 98, 5/21, p 20 799Google Scholar
  24. 24.
    Salusky IB, Coburn JW, Nelson P, Goodman WG (1990) Prospective evaluation of aluminum loading from formula in infants with uremia. J Pediatr 116:726–729Google Scholar
  25. 25.
    Tsou VM, Young RM, Hart M, Vanderhood J (1991) Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum. Pediatrics 87:148–151Google Scholar
  26. 26.
    Salusky IB, Foley J, Nelson P, Goodman WG (1991) Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 324:527–531Google Scholar
  27. 27.
    Driscoll CT Jr, Baker JP Bisogni JJ, Schofield CL (1980) Effect of aluminum on speciation on fish in dilute acidified waters. Nature 284:161Google Scholar
  28. 28.
    Slanina P, Frech W, Ekstrom, L, Luof L, Slorach S, Cedegren A (1986) Dietary citric acid enhances absorption of aluminum in antacids. Clin Chem 32:539Google Scholar
  29. 29.
    Karlik SJ, Eichhorn GL, Lewis PN, Crapper DR (1980) Interaction of aluminum species with DNA. Biochemistry 19:5991Google Scholar
  30. 30.
    Greger JL, Baier MJ (1983) Excretion and retention of low or moderate levels of aluminum by human subjects Fd Chem Toxic 21:473Google Scholar
  31. 31.
    Kaehny WD, Hegg AP, Alfrey AC (1977) Gastrointestinal absorption of aluminum from aluminum-containing antacids. N Engl J Med 296:1389Google Scholar
  32. 32.
    Alfrey AC (1980) Aluminum metabolism in uremia. Neurotoxicology 1:43–53Google Scholar
  33. 33.
    Alfrey AC (1986) Aluminum metabolism. Kidney Int 29:S8Google Scholar
  34. 34.
    Sjögren B, Lunbgerg I, Lidums V (1983) Aluminum in the blood and urine of industrially exposed workers. Br J Ind Med 40:301Google Scholar
  35. 35.
    McLaughlin AIG, Kazantzis G, King E, Teare D, Porter RJ, Owen R (1962) Pulmonary fibrosis and encephalopathy associated with aluminum dust. Br J Ind Med 19:253Google Scholar
  36. 36.
    Alfrey AC (1983) Aluminum. Adv Clin Chem 123:69–91Google Scholar
  37. 37.
    Bozynski MEA, Sedman AB, Naglie RN, Wright EJ (1989) Serial plasma and urinary aluminum levels and tissue loading in preterm twins. J Parenter Enter Nutr 13:428–431Google Scholar
  38. 38.
    Polinsky MS, Prebis JW, Elzouki AE (1980) The dialysis encephalopathy syndrome in childhood: results of a survey to determine incidence and geographic distribution of cases. Proceedings of the Chronic Renal Disease Conference, National Institutes of Arthritis, Metabolism, and Digestive Diseases, BethesdaGoogle Scholar
  39. 39.
    Sedman AS, Wilkening G, Warady BA, Lum GM, Alfrey AC (1984) Encephalopathy in a child secondary to auminum toxicity. J Pediatr 105:836–838Google Scholar
  40. 40.
    Moreno A, Dominquez P, Dominquez C, Ballabriga A (1991) High serum aluminum levels and acute reversible encephalopathy in a 4 year old boy with acute renal failure. Eur J Pediatr 150:513–514Google Scholar
  41. 41.
    Salusky IB, Coburn JW, Brill J (1988) Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD. Kidney Int 33:975–982Google Scholar
  42. 42.
    Koo WWK, Kaplan LA, Bendon R, Succop P, Tsang RC, Horn J, Steichen JJ (1986) Response to aluminum in parenteral nutrition during infancy. J Pediatr 109:877Google Scholar
  43. 43.
    Vileisis RA, Klein GL, Alfrey AC (1988) Lack of effect of furosemide on aluminum excretion in preterm parenterally nourished infants. Clin Res 36:77AGoogle Scholar
  44. 44.
    Freundlich M, Zilleruelo G, Abitol C, Strauss J (1985) Infant formula as a cause of aluminum toxicity in neonatal uremia. Lancet II:527–529Google Scholar
  45. 45.
    Hallerstein S and Committee on Nutrition (1986) Aluminum toxicity in infants and children. Pediatrics 78:1150–1154Google Scholar
  46. 46.
    Ellis HA, McCarthy JH, Herrington J (1979) Bone aluminum in hemodialyzed patients and in rats injected with aluminum chloride: relationship to impaired bone mineralization. J Clin Pathol 32:832Google Scholar
  47. 47.
    Goodman WG, Henry DA, Horst R, Nudelman RK, Alfrey AC, Goodman JW (1984) Parenteral aluminum administration in the dog: induction of osteomalacia and effect of Vit D metabolism. Kidney Int 25:370Google Scholar
  48. 48.
    Sedman AB, Alfrey AC, Miller NJ, Goodman WG (1987) Tissue and cellular basis for impaired bone formation in aluminum related osteomalacia in the pig. J Clin Invest 79:86Google Scholar
  49. 49.
    Talwar HS, Reddi AH, Menczel J, Thomas WC Jr, Meyer JL (1986) Influence of aluminum on mineralization during matrix induced bone development. Kidney Int 29:1038Google Scholar
  50. 50.
    Alfrey AC (1985) The case against aluminum affecting parathyroid function. Am J Kidney Dis VI:309–312Google Scholar
  51. 51.
    Andreoli SP, Smith JA, Bergstein JM (1985) Aluminum bone disease in children: radiographic features from diagnosis to resolution. Radiology 156:663–667Google Scholar
  52. 52.
    Elliot HL, Dryburgh F, Fell GS (1978) Aluminum toxicity during regular hemodialysis. BMJ 1:1101–1103Google Scholar
  53. 53.
    Kaiser L, Schwartz KA (1985) Aluminum-induced anemia. Am J Kidney Dis VI:348–352Google Scholar
  54. 54.
    Shah NR, Oberkircher OR, Lobel JS (1990) Aluminum-induced microcytosis in a child with moderate renal insufficiency. Am J Pediatr Hematol Oncol 12:77–79Google Scholar
  55. 55.
    Crapper McLanchlan DR, Kruck TP, Lukiw JW, Krishnan SS (1991) Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease? Can Med Assoc J 145:793–804Google Scholar
  56. 56.
    Crapper DR, Dalton AJ (1973) Alterations in short term retention, conditioned avoidance response acquisition and motivation following aluminum induced neurofibrillary degeneration. Physiol Behav 10:925–933Google Scholar
  57. 57.
    Crapper DR, Dalton AJ (1973) Aluminum induced neurofibrillary degeneration brain electrical activity and alterations in acquisition and retention. Physiol Behav 10:935–945Google Scholar
  58. 58.
    Crapper DR (1973) Experimental neurofibrillary degeneration and altered electrical activity. Electroencephalogram. Clin Neurophysiol 35:575–588Google Scholar
  59. 59.
    Foley CM, Polinsky MS, Gruskin AB, Baluarte HJ, Grover WD (1981) Encephalopathy in infants and children with chronic renal disease. Arch Neurol 38:636–658Google Scholar
  60. 60.
    Rotundo A, Nevins TE, Lipton M, Lockman LA, Mauer SM Michael AF (1982) Progressive encephalopathy in children with chronic renal insufficiency in infancy. Kidney Int 21:486Google Scholar
  61. 61.
    Tagge EP, Campbell DA, DaFoe DC, Merion RM, Sedman AB, Kelsch RC, Mollen E, Rocher LL, Turcotte JG (1987) Pediatric renal transplantation with an emphasis on the prognosis of patients with chronic renal insufficiency since infancy. Surgery 102:692–698Google Scholar
  62. 62.
    Geary DF, Haka-Ikse K (1989) Nerodevelopmental progress of young children with chronic renal disease. Pediatrics 84:68–72Google Scholar
  63. 63.
    Andreoli SP, Chesney RW, Salusky IB, Sedman AB (1990) Ask the expert (invited questions from the editor). Pediatr Nephrol 4:318Google Scholar
  64. 64.
    Warady BA, Ford DM, Gaston CE, Sedman AB, Huffer WE, Lum GM (1986) Aluminum intoxication in a child: treatment with intraperitoneal deferoxamine. Pediatrics 78:651–655Google Scholar
  65. 65.
    Molitoris BA, Alfrey PS, Miller NL, Hasbargen JA, Kaehny WD, Alfrey AC, Smith BJ (1987) Efficacy of intramuscular and intraperitoneal deferoxamine for aluminum chelation. Kidney Int 31:986–991Google Scholar
  66. 66.
    Martis L, Serkes KD, Nolph KD (1989) Calcium carbonate as a phosphate binder: is there a need to adjust peritoneal dialysate calcium concentrations for patients using CaCO3? Peritoneal Dial Int 9:325–328Google Scholar
  67. 67.
    Mai ML, Emmett M, Sheikh MS, Santa Ana C, Schiller L, Fordtran JS (1989) Calcium acetate, an effective phosphorus binder in patients with renal failure. Kidney Int 36:690–695Google Scholar
  68. 68.
    Nolan CR, Califano JR, Butzin CA (1990) Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int 38:937–941Google Scholar

Copyright information

© IPNA 1992

Authors and Affiliations

  • Aileen Sedman
    • 1
  1. 1.Department of PediatricsUniversity of Michigan Medical CenterMIAnn ArborUSA

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