Dialysis dementia causes

Aluminium toxicity is the likely cause of three human disorders arising from long-term haemodialysis vitamin D-resistant osteomalacia, iron adequate microcytic anaemia, and dialysis dementia (Martin, 1994). The first of these conditions is consistent with interference with calcium deposition into bone, and the accumulation of aluminium in the bone matrix. 

The neurotoxic effects of aluminum were first observed in people undergoing dialysis for treatment of kidney failure. This syndrome, called dialysis dementia, starts with speech disorders and progresses to dementia and convulsions. Symptoms corresponded with elevated aluminum levels commonly found in bone, brain, and muscle following 3 to 7 years of treatment. Elevated levels of aluminum were also found in the brains of people suffering from Alzheimer s disease. Despite considerable research, it is not clear if the aluminum accumulation in the brain is a cause of Alzheimer s disease or a result of changes in the brain associated with the disease. 

Bioinorganic chemistry will surely develop in an even wider area than it has thus far. Attention is likely to increase for studies on nonmetals, such as Se and As and their roles in, e.g., detoxification reactions. In addition, studies on elements such as aluminum (a possible causative factor in dialysis dementia and related to Alzheimer disease, senile dementia) and other abundant earth crust metals will increase. The role of bioinorganic catalysis to make and keep our environment clean has been mentioned in many of the previous chapters. It is to be expected that future catalytic processes, based on and derived from biological ones, will be as clean as possible, producing useful, harmless, and biodegradable products for the world. 

Flendrig JA, Kruis H, Das HA. 1976. Aluminum intoxication The cause of dialysis dementia Proc Eur Dial Transplant Assoc 13 355-363. 

Elevated aluminum levels have been implicated as the cause of dialysis encephalopathy or dementia in renal failure patients undergoing long-term hemodialysis [85]. Some patients used aluminum-containing medications. Moreover, patients with renal failure cannot remove aluminum from the blood. Dialysis dementia can arise after three to seven years of hemodialysis treatment. Speech disorders precede dementia and convulsions. Since many hemodialysis units rely on systems to purify fluoridated tap water, it is likely that many patients are being exposed inadvertently to increased concentrations of fluoride and aluminum. Increased serum fluoride concentration and fluoride intoxication have been also observed in chronic hemodialysis patients. Arnow et al. [96] reported that 12 of 15 patients receiving dialysis treatment in one room became acutely ill, with multiple non-specific symptoms and fatal ventricular fibrillation. Death was associated with longer hemodialysis time and increased age compared with other patients who became ill. 

In the same decade, five dialysis patients developed dyspraxia and seizures at a dialysis center in Denver, Colorado (Alfrey et al. 1972). Investigators suspected a contaminant in the tap water used for dialysis but did not suspect aluminum until their second study in 1976 found increased aluminum in the gray matter of 12 subjects with dialysis dementia (DD) (Alfrey et al. 1976). Two fields of research then merged with additional data from occupational exposures to focus on aluminum s putative role as a cause of dementing illnesses. 

Many other possible causes of dialysis dementia have been proposed. These inclnde other trace element contaminants, normal pressure hydrocephalus, slow virus infection of the central nervous system, and regional alterations in cerebral blood flow (Arieff, 1990). Slow virus infection of the nervous system is a possible etiology for dialysis dementia. The clinical manifestations resemble those of other slow virus infections, such as Kuru or Creutzfeldt-Jakob disease (Selkoe, 1978 4714 Gajdusek, 1985 1662). 

Patients with dialysis dementia respond positively to an antibody against the hyperphosphorylated microtubule-associated protein, tau, that accumulates in AD tangles (Guy et al. 1991). The neurofilament protein tubulin contains an acidic tau binding site to which Al might bind to cause tau accumulation. However, not only do dialysis dementia patients characteristically show no tangle formation, but the tangles seen in animals treated with Al are predominantly made up of neurofilament subunits such as tubulin, rather than microtubule-associated protein. A potential role for Al in G-protein-regulated neurofilament polymerization is discussed in Sect. G. 

Flendrig JA, Kruis H, Das HA (1976) Aluminium intoxication the cause of dialysis dementia Proc Eur Dial Transplant Assoc 13 355-361 Froment DPH, Molitoris BA, Buddington B, Miller N, Alfrey AC (1989) Site and mechanism of enhanced gastrointestinal absorption of aluminium by citrate. Kidney Int 36 978-984... 

In contrast to the nuclear binding of aluminum in senile dementia, the aluminum in dialysis dementia patients has been reported to be primarily cytoplasmic. This is of particular interest, for in dialysis dementia patients, neurofibrillary tangles have not been observed to accompany increased aluminum concentrations. It is tempting to speculate that the differential cellular responses to aluminum might be caused by different binding sites for aluminum within the ceU. 

Since 1976, aluminium has been known to be a cause of encephalopathy, a potentially fatal condition occurring primarily in patients on chronic dialysis (21). Difficulties in speech, disturbances of consciousness, and ataxia can be followed by psychotic episodes, personahty changes, myoclonic jerks, electroencephalographic abnormalities, convulsions, and dementia. Accumulation of aluminium can be demonstrated in the gray matter of the brain and in other tissues. If not too advanced, the condition can recede after reduction of aluminium intake and use of deferoxamine. 

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