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Contr. Nephrol., vol. 38, pp. 47-58 (Karger, Basel 1984)

Epidemiology of Aluminium Toxicity in a

Low Incidence

Area

R.J. Winney 1.F. Cowie

A D

Cumming

A I K

Short

G.D. Smith 1.S. Robson

Medical Renal Unit, Department of Medicine and Department of Pathology,

Royal Infirmary, Edinburgh, Scotland,

UK

Introduction

Following the observation by Alfrey

et

al. [ ] that encephalopathy in

patients with chronic renal failure might result from aluminium toxicity,

the evidence in favour of an aluminium toxicity syndrome, particularly in

patients treated by haemodialysis, has accumulated rapidly [2-10]. The

major source

of

aluminium in haemodialysis patients is the water used for

dialysis [5], but the oral ingestion of aluminium hydroxide as a phosphate

binder, while rarely being the sole cause of clinical toxicity [11], also contri

butes to accumulation in these patients

[12-13].

While most reports of

aluminium toxicity have arisen from centres with very high aluminium con

centrations in the water [2,

5, 7-10 14] it seems unlikely that this problem

is confined to such areas since aluminium transfer to the patient during

haemodialysis occurs at very low concentrations in the dialysis fluid

[15-17].

In a survey of British dialysis centres, Edinburgh had a low incidence

of both encephalopathy and fracturing osteodystrophy [14]. However, fol

lowing the development of encephalopathy in a home dialysis patient in

1977 an analysis of water supplies revealed considerable variation in water

aluminium, although the levels were much lower than in areas with a high

incidence

of

clinical toxicity. As a result we began a longitudinal study

of

plasma, water and dialysate aluminium in haemodialysis patients with the

aim

of

defining the degree

of

aluminium accumulation in our patients and

relating this to water and dialysis fluid aluminium as well as to possible clin

ical sequelae.

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Winney/Cowie/Cumming/Short/Smith/Robson

48

Patients and Methods

87 patients treated by intermittent haemodialysis were studied. At the start of the study

there was no water treatment

in

the 37 patients treated by hospital haemodialysis and in the

remainder, who were treated by home haemodialysis, the water was softened.

After an initial period of monitoring and, as a result of the initial findings, reverse os

mosis wate r treatment was introduced if needed to maintain the dialysate aluminium 1

lmoll . Following this the patients could be divided into three groups. In the 37 patients in

group 1

on

hospital haemodialysis (age 45.4

11.6 years) water t reatment was changed from

no

treatment

to reverse osmosis. In the 27 patients in group 2 on home haemodialysis (age

47.4 12.2 years) water tr eatment was changed from softening to reverse osmosis. In the 23

patients in group 3

on

home haemodialysis (age 46.2 10.7 years) water was

treated

by sof

tening throughout the duration

of

the study.

Haemodialysis was conducted using a proportionating system with dialysate flow of 500

mllmin and either Cordis Dow 1.3 m

2

, Asahi AM.lO 1.1 m

2

or

Gambro

Lundia 1 1 m

2

dialys

ers. Patients treated by the Redy system were excluded from the study. Patients on hospital

haemodialysis were treated for

5 7

h twice weekly and

on

home haemodialysis for 5 h

three times weekly. All patients were prescribed aluminium-containing phosphate binders if

indicated

to

maintain the plasma phosphate 2 mmol/ .

Untreated water and dialysate aluminium were measured monthly. In patients on hospi

tal treatment plasma aluminium was measured monthly while in home patients estimations

were performed at outpatient visits (one to three monthly).

Aluminium was analysed in duplicate samples of water, dialysis fluid and plasma by

atomic absorption spectrophotometry using the Perkin Elmer 127 spectrophotometer with

HGA carbon furnace [18). The method was modified for dialysis fluid and plasma by using a

continuous ramp time between

120

and 1 400C and a total time between these temperatures

of 18 s No significant difference was found in aluminium analysis using standards with

acidified m/soo nitnc acid) water compared with acidified saline standards. Thus any signal

suppression by sodium was slight and statistically insignificant. Similarly no significant differ

ence was found when aluminium was analysed using plasma

or

serum.

In our laboratory for

29

normal people the plasma aluminium was 0.2

0.07 lmol/ . In

15 patients with chronic renal failure who were not on dialysis

and

not

treated

with aluminium

containing phosphate binders the plasma aluminium was 0.47

0.39 lmolll;

in

a further group

of 30 patients with chronic renal failure also not on dialysis but treated with aluminium-con

taining phosphate binders the plasma aluminium was 1.32

0.7 lmolll.

For

each patient the mean water, dialysate and plasma aluminium during each method

of water treatment was calculated to give an index of overall exposure. These results were

then used

to

calculate the mean values for each group. Values in tables and text are expressed

as the mean 1 SO.

Results

Before Introduction o Reverse Osmosis

There was marked variation in water aluminium in groups 1 and 2 with

levels fluctuating from one week to another (table I.) Exposure to

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Aluminium Toxicity in a Low Incidence Area

49

able

/.

Results of aluminium monitoring in haemodialysis patients before and after change

to reverse osmosis RO) water treatment

Group Number Total

Water Duration of Mean

of duration treatment observation water

patients haemodialysis months aluminium

months

I Imolll

37

44.2 5.5

none 3.6 0.9 5.6 1.99

RO

19.2 10.2

2

27

89.3 33.1

softening

12.4 6.3

2.11.5

RO

23.3 7.8 2.6 1.9

3

23 71

25.2

softening

36.3 9.3 0.7 0.2

Group Number Mean dialysate

Mean plasma Clinical

of aluminium aluminium toxicity

patients

I Imol/l I Imolll

(number of patients)

37

2.3 1.5 8.2 4.6 9

0.4 0.1 4.9 2.8

2

27

1.1

0.7 6.4 3.1 7

0.6 0.2

5.3 0.4

3

23 0.6 0.2

3.9 1.2 0

aluminium within each group was reflected equally by either water, dialy-

sate

or

plasma aluminium which were all highest in group 1 with no water

treatment, intermediate in group 2 and lowest in group 3 (table I). The in-

cidence of clinical toxicity was also related to the degree of exposure to

aluminium

as

assessed by either water, dialysate or plasma aluminium

(table I). The plasma aluminium in group 3 was significantly lower than

that in group 1 (p 0.001) despite the significantly longer duration of

dialysis than patients in group 1 (p 0.001). For the 50 patients treated by

water softening there was a significant correlation between plasma and

dialysate aluminium (fig. 1)

as

well

as

between plasma and water

aluminium (r 0.35; p 0.02). By contrast no correlation existed between

plasma aluminium and duration of dialysis in any group. In groups 1 and 2

the plasma aluminium in patients with clinical toxicity was significantly

higher than that in patients without toxicity (table II).

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Winney Cowie Cumming Short Smith Robson

14-

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Mean

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50

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1.

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haemodialysis using softened water. r

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