Prevention and Management Al Intoxication

Because Al toxicity is a serious iatrogen complication, any preventive measures to avoid exposure to Al are incumbent. Unfortunately, with the current treatment practices, there continues to be a risk that patients receive excessive amounts of Al orally or parenterally. If Al compounds cannot be avoided in patients with renal failure, routine Al tests performed every 3-4 months in serum will identify persons at greatest risk (s-Al levels > 100 to 150 µg/L) for chronic Al intoxication. Ideally, any patient with s-Al higher than 40 to 50 mg/L should discontinue Al gels and use other substitutes. These patients should also be warned not to ingest these compounds with liquids containing citrate, for example, fruit juices.

Hemodialysis patients in dialysis centers or on home hemodialysis generally will be protected from Al intoxications by the combination of deionization and RO devices. Nevertheless, one should realize that the composition of the dialysate is a combination of "normal" drinking water according to WHO guidelines and extended water purification. Drinking water conditions can change unexpectedly and erratically at the water plant as well as in the water distribution system, making it absolutely unsuitable for preparation of dialysate upon its arrival in the dialysis unit without optimal further water treatment. Especially Al concentrations in the water supply in regions that use Al salts for purification can vary from day to day and it is impossible to monitor the water Al levels frequently enough to detect periodic but dangerous increments in Al levels.

Physicians in charge of dialysis centres should be aware of the fact that they are solely responsible for the water quality of the dialysate63 _{and that the} conditions of the water treatment system can change, especially due to Al compounds in the water supply. Membrane fouling in reverse osmosis (RO) systems is inevitable in many systems and effectively anticipating, compensating for and counteracting the fouling phenomena is necessary. While overall flux performances will decline for all membrane systems, the actual time between cleanings will vary, depending upon membrane type, system design and feed water quality. Reverse osmosis is an effective means of removing a wide spectrum of contaminants, including particles, inorganic substances, organic chemicals with molecular weight greater than 300, bacteria and endotoxins. An important exception to this general rule relates to Al, which, because of its amphoteric nature, may be present as a non-ionized species. In such circumstances, deionisation with mixed bed units may be ineffective for Al removal and reverse osmosis may be superior to deionisation. Other factors, especially scalants, can also reduce the quality of the RO membranes. The two most common scalants are calcium carbonate and calcium sulfate. Sharply pointed scale crystals may come into contact and cut the membrane, causing irreversible damage. Well-known fouling particles besides bacteria are Al, iron and silica.259_{Although in a review in the 1980s 92% of reported dialysis dementia} cases were dialyzed with either unprocessed or softened water, still 6% of dialysis dementia patients were treated with water prepared by either deionisation or reverse osmosis until the 1990s.46_{Even dialysis centres with sophisticated water treatment} devices may be faced with episodes of serous Al intoxication, due to the use of Al salt coagulants in potable water treatment. The scarce rainfall in the South of Portugal in 1992 resulted in a subsequent decrease in the level of water sources, resulting in high concentrations of suspended particles, which, in turn, necessitated the addition of huge amounts of alum. This action was not reported to the municipal authorities. In a dialysis centre in Portugal using a RO, the passage of this severely contaminated water through the water purification installation of a hemodialysis centre resulted in the obstruction of the RO membranes.30,43-45_The efficiency of the RO membranes relies on two rejection mechanisms: a mechanical sieving filter with 200 Dalton pores and an electrostatic repulsive mechanism. The ionized Al fraction is rejected very efficiently (up to 99%) by the RO membranes. However, for the bulk Al, present as a colloid, the RO membranes get fouled.

Membrane fouling does enhance the accumulation of concentration at the membrane level and masks the electrostatic repulsion mechanism. This is matched with an increased Al breakthrough. In these circumstances, it has been found that the ability of the RO to reject Al may become as low as 30% to 50%. Consequently, RO membranes and cartridge filters had to be replaced frequently. During these interventions, which took place over a period of several days, insuffi- ciently treated water was sent directly to the dialysis machines and to the patients involved. In this case both ways of exposure probably contributed to acute Al intoxication and all together 18 of 71 (25.3%) patients died of severe encephalopathy.30,43,44_{Al levels up to 2,200 µg/L were measured in water used for} preparation of the dialysate.45 _{Most RO units, however, make use of continuous} conductivity monitoring of the purified water. A low conductivity represents a low amount of dissolved ions, which means that the membranes are functioning well. Nevertheless, in some cases one series of RO membranes may be insufficient which makes two RO membranes in line necessary.260

It should be stressed that regular monitoring of the Al levels in serum and dialysate at the normal frequency of one to three times a year,62_{might give a false} sense of reassurance when the results are normal, as serious exposure might be unnoticed between these testing intervals and serious irreversible neurological damage can develop within weeks. Additional safety precautions can result from a good cooperation between drinking water companies and dialysis centres. Water utilities should notify dialysis centres when situations with important changes in water quality are expected. In particular, dialysis centres should be warned when the Al concentration in drinking water can exceed 30 µg/L. This implies that the dialysis centres should be informed when water utilities change the practice of flocculation to the use of Al flocculants. The centres should also be informed if the concentration of Al exceeds the relatively high level of 200 µg/L, above the WHO standards. In addition, when cemented drinking water distribution pipes are put into service, Al levels should be tested in the tap water and dialysis centres should be warned when Al levels are above 30 µg/L.18