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KIDNEY patients in Britain are again at the focus of research into aluminium
poisoning. Å®ÉúСÊÓƵs have found abnormalities in the way that the brain
responds in patients whose blood contains only moderately raised amounts
of the metal compared with other kidney patients. Although the people examined
by the scientists appeared to be mentally well, their performance in a range
of tests was worse than that of a group of normal people who acted as controls,
and their brains reacted more slowly to specific visual stimuli.

The new work, by Paul Altmann at the London Hospital and his colleagues
at the University of Aston in Birmingham, renews the debate on how poisonous
aluminium is (The Lancet, vol ii 1989, p 7). It suggests that even when
there is no overt sign of poisoning, the metal is doing damage to the brain.

As early as 1980, Peter Ackrill, Jane Barron and others at the Withington
Hospital in Manchester showed that kidney patients who appeared well to
their doctors and their relatives had distinctive abnormalities that speech
therapists could recognise in the way that they spoke (British Journal of
Disorders of Communication, vol 15, p 75). However, these patients had been
exposed to much higher levels of aluminium than Altmann’s patients – water
used for their dialysis at that time contained up to 650 micrograms of the
metal per litre.

Since 1980, however, techniques for measuring aluminium in the body
have improved, enabling researchers to make more quantitative assessments
of the state of their patients. Ackrill and his colleagues are continuing
their research on disorders of speech as a marker for early damage from
aluminium. Altmann’s team, on the other hand, has looked at biochemical
signs of deterioration, objective tests of cerebral function, and the electrical
activity of the brain. Both teams agree that doctors must be still more
stringent in controlling the amount of aluminium that enters a patient’s
body. ‘It’s clearly a much more toxic element than people realise,’ says
Altmann.

Since the 1970s, researchers have known that, without careful monitoring,
kidney patients risk fatal brain damage and dementia, bone disease and anaemia
because of the large amounts of aluminium that they can encounter.

Kidney patients are exposed to aluminium from two sources. First, people
whose kidneys malfunction often need to take medicines which contain aluminium
in order to bind phosphates that they could not otherwise excrete. In a
day, a patient may take more than a gram of aluminium in these medicines,
whereas a normal diet contains less than 2 milligrams a day. Some of the
metal in the medicines is in a soluble form and can, therefore, enter the
bloodstream.

Secondly, most kidney patients must have regular dialysis to remove
wastes and toxins from the body. In dialysis, blood from the patient passes
through an artificial kidney. The waste materials in the blood pass across
a semipermeable membrane into a fluid kept separate from the body, then
the ‘cleaned’ blood returns to the body. A four-hour session on a dialysis
machine will expose a patient to 120 litres of water.

Health authorities treat the tap water used to prepare the fluid for
dialysis, in order to remove the large and variable quantities of aluminium
that it may contain. If the treated water contains more than 14 micrograms
of aluminium per litre, however, some will pass into the patient (This Week,
21 January).

Altmann worked with a group of 27 patients who had, on average, 59 micrograms
of aluminium per litre of blood. This level is high for a normal person
but levels between 60 and 80 micrograms per litre are common in kidney patients,
says Altmann. In extreme cases, a patient who has been on dialysis and aluminium
medicines regularly for several years may have several hundred micrograms
of aluminium per litre in their blood.

Altmann’s group of patients had had regular dialysis for seven years.
He stresses that none of them was chronically demented. All appeared mentally
well. However, when he asked 27 patients to do various computerised psychological
tests – such as matching shapes with digits – their responses were significantly
less accurate and slower than those of the control group.

In addition, the researchers tested 10 patients by measuring the electrical
activity of their brains while they gave them visual stimuli from flashing
lights and a reversing pattern. Their responses to pattern were as rapid
as a normal person’s, but their responses to the flash were significantly
delayed compared with those of the control group.

Another of Altmann’s tests involved an enzyme called erythrocyte dihydropteridine
reductase (DHPR). This enzyme is involved in the production of certain neurotransmitters
in the brain, and researchers can measure it in the blood. Altmann has shown
that aluminium inhibits DHPR, and that the enzyme becomes more active if
aluminium is removed. Because the enzyme is present both in the brain and
the blood, it may provide a useful marker for what is going on in the brain,
says Altmann.

He gave 15 of the patients at the London Hospital a drug called desferrioxamine
(DFO) which doctors can use to remove aluminium. DFO works by binding aluminium
and effectively drawing it out of the tissues into the blood. Dialysis then
removes it from there. However, it may take many months to remove the metal
that the patient has accumulated.

Altmann found that, after three months of treatment with DFO, the patients’
levels of DHPR rose by an average of 51 per cent. The group also performed
better in some of the mental tests than they had before treatment. There
is good evidence that the two findings were directly linked, says Altmann,
although he adds that there is no proof.

Ackrill in Manchester was the first to use DFO for patients with aluminium
poisoning. One patient with apparently terminal brain disease and very high
levels of aluminium in his blood recovered after treatment with the drug
in 1979, and is still alive and well a decade later. Doctors are using the
drug increasingly to treat thousands of kidney patients who suffer from
bone disease caused by aluminium poisoning, although the treatment carries
certain risks.

The results of the new research suggest that ‘much more rigorous exclusion
of aluminium from the dialysate and diet of dialysis patients is necessary’.
Altmann considers that the tests of cerebral activity may be useful ways
of monitoring patients regularly to detect the earliest signs of brain damage.

He also raises the question of whether the research could give scientists
new clues about the development of Alzheimer’s disease – a form of dementia
that other researchers have linked with aluminium (This Week, 21 January).

‘Although patients on dialysis don’t have a higher rate of Alzheimer’s
than the general population, it is interesting to ask whether our patients
represent some sort of model for Alzheimer’s,’ says Altmann. The specific
disturbance in the brain’s response to the visual stimuli in the patients
was very similar to that seen in the brains of people with Alzheimer’s.

Meanwhile, Ackrill is cautious about the usefuleness of measuring aluminium
levels in the blood alone. This is because so much of the metal may be stored
in the tissues, only to be mobilised at some later stage. He believes that
researchers need a much better way of measuring total aluminium levels before
they can tell if someone is ‘overtly toxic’ or not.

Both teams agree, however, that the priorities are to find a satisfactory
alternative to medicines that contain aluminium – at present, there is none
– and to persuade water companies to stop treating water with aluminium
sulphate.