Dementia dialysis

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. 

Epidemiological studies have shown a strong association between the aluminum content of the water used to prepare dialysates and the incidence of dialysis dementia. Reducing water aluminum content below 20 JJ.g/1 appears to prevent the onset of the disease in patients who have just started dialysis. 

Aluminum (Al) Dialysis dementia During dialysis, food, drinking water,... 

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. 

Complexation of Zn11 with ATP results in a significant shift of the H-8 resonance which is taken as evidence of Zn binding to the N-7 atom. The effect of coordination on the C(8)-H bond also explains the formation of a metal-C(8) bond with the MeHg+ ion.120 Multinuclear NMR has been used to identify a number of Al111 complexes of ATP in solution, and the results related to the involvement of Al in dialysis dementia disease.121... 

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. 

The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients had an increased body burden of aluminum. The decreased renal function and loss of the ability to excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Pre-term infants may also be particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991)... 

Banks WA, Kastin AJ. 1983. Aluminum increased permeability of the blood-brain barrier to labelled DSIP and beta-endorphin Possible implications for senile and dialysis dementia. Lancet 2 1227-1229. 

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

In the past several clinical patterns have been described. The most important recognized clinical patterns or types of Al toxicity include two types of encephalopathy. Firstly, the classical dialysis dementia sometimes referred to as dialysis encephalopathy syndrome (DES) or dementia dialytica [24, 28, 37, 42, 70-74] and secondly, the acute or subacute Al encephalopathy [41]. There are also two types of bone disease - either osteomalacia with bone fractures and proximal myopathy or aplastic bone disease [41, 75, 76]. There is quite some confusion in the definitions of Al toxicity in the literature. Because there seems to be an obligatory lag phase of at least several days to weeks for symptoms to occur, acute Al encephalopathy, defined as a direct result of a single overdose, probably does not exist. Because of the long lag phase of several months to years necessary to develop the chronic dialysis encephalopathy and also because acute Al encephalopathy has an abrupt, sudden onset of symptoms one can understand why the term acute is used instead of the more descriptive subacute . The descriptions dialysis dementia [37, 42, 46, 73, 74] and dialysis encephalopathy [33-36, 38, 40, 41, 78] are also unfortunate because true dementia is rare in Al encephalopathy [73] and non-dialyzed patients can also develop these symptoms [78]. There are also many dialysis-related encephalopathy syndromes unrelated to Al. As an example,... 

Clinical Symptoms of Acute Al Encephalopathy and Chronic Al Encephalopathy (also Referred to as Classical "Dialysis Dementia")... 

Davidson et al. found that the cumulative risk of death due to dialysis dementia in patients whose water supply had a mean Al concentration >200 pg/L was significantly greater (27.9% deaths in the first 40 months) than the risk in patients whose mean water Al content was <200 pg/L (2.1% deaths in the first 490 months). The relation between the mean Al concentration in the dialysate and time to death was given in the formula [24] The time in months from the first symptoms of dialysis dementia to death = 65—0.081 x [mean Al concentration (pg/L) in dialysis water]. 

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. 

Toxic disorders Drug, narcotic, heavy metals Organic toxins Medications (prescription) Alcohol consumption Dialysis dementia (aluminum) Removal of offending toxin... 

He was hospitalized for revision of his arteriovenous shunt and postoperatively complained of symptoms of gastroesophageal reflux. This complaint prompted institution of cimetidine therapy. In view of the patient s impaired renal function, the usually prescribed dose was reduced by half. Three days later, the patient was noted to be confused. An initial diagnosis of dialysis dementia was made and the family was informed that dialysis would be discontinued. On teaching rounds, the suggestion was made that cimetidine be discontinued. Two days later the patient was alert and was discharged from the hospital to resume outpatient hemodialysis therapy. 

Sideman S, Manor D. The dialysis dementia syndrome and aluminum intoxication. Nephron 1982 31(1) 1-10. 

The use of deferoxamine to reduce aluminium overload in hemodialysis patients can exacerbate aluminium encephalopathy and precipitate dialysis dementia (30-34). Confusion, disorientation, agitation, aggression, abnormal behavior, speech arrest, myoclonus, hallucinations, and seizures can occur. Some patients are very sensitive to this effect, and a test dose of deferoxamine is advisable in order to ascertain whether aluminium is excessively mobilized (35). 

Sherrard DJ, Walker JV, Boykin JL. Precipitation of dialysis dementia by deferoxamine treatment of aluminum-related bone disease. Am J Kidney Dis 1988 12(2) 126-30. 

Furthermore, certain factors may increase intestinal aluminum absorption. We have previously described severe hyperaluminemia resulting in an acute rapidly fatal encephalopathy in four uremic patients who had been taking aluminum hydroxide and Shohl s solution, an alkalinizing buffer of sodium citrate and citric acid. The encephalopathy resembled the earlier dialysis dementia of the 1970s, but was much more acute, culminating in death within 3 weeks (B4, B5). 

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. 

J Neurol Neurosurg Psychiatry 39 411-419, 1976 Chui HC, Damasio AR Progressive dialysis encephalopathy ( dialysis dementia ). J Neurol 222 145-157, 1980... 

Rozas VV, Port FK, Easterling RE An outbreak of dialysis dementia due to aluminum in the dialysate. Journal of Dialysis 2 459-470, 1978a Rozas W, Port FK, Rutt WM Progressive dialysis encephalopathy from dialysate aluminum. Arch Intern Med 138 1375-1377, 1978b Scherp HW, Church CF Neurotoxic action of aluminum salts. Proc Soc Exp Biol Med 36 851-853, 1937... 

Ball JH, Butkus DE, Madison DS Effect of subtotal parathyriodectomy on dialysis dementia. Nephron 18 151-155,1977... 

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