Aluminium and bone disease in chronic renal failure.
Aluminium is absorbed by the intestines and is rapidly transported into bone, where it disrupts mineralization and bone cell growth and activity. Its toxicities result in or exacerbate painful forms of renal osteodystrophy, most notably adynamic bone disease and osteomalacia, but also other forms of the disease. Because aluminium is sequestered in bone for long periods, its toxic effects are cumulative. As a result, even intermittent or low-dose use of aluminium-based phosphate binders adds to the total load of this toxin in the bone; thus, aluminium use is inadvisable, even for a 'rescue indication'. Aluminium blood levels are not a reliable marker of aluminium absorption or organ load in dialysis patients: only stainable aluminium at the mineralization front reflects the histopathological changes observed in bone. Therefore, bone biopsies remain the only approach for definitive diagnosis of aluminium-related bone disease. Most importantly, lack of correlation between overall organ concentrations of a toxin, such as aluminium, and pathological changes does not rule out toxicity. Thus, the specific localization of the toxin is more important than overall organ concentration. What has been observed with aluminium during 25 years of research might be reproduced with other metals that are absorbed, transported and accumulated in bone. What we have learned about the toxicity of aluminium should inform our interpretation of data from studies of other metal-based therapeutics for renal patients. This calls for careful evaluation of any newly introduced therapeutic agents for bone disease in patients lacking excretory kidney function.
Malluche
Hartmut H
HH
University of Kentucky, Division of Nephrology, Bone and Mineral Metabolism, Lexington, 40536-1052, USA. hhmall@uky.edu
D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity; D001847:Bone Diseases / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*
D000535:Aluminum