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Why Do Aluminum Analyses?
Based on the author's experience as a dialysis laboratory director, several types of abnormal blood aluminum results which may be encountered are presented. Their various interpretations are discussed. Conclusions are drawn for recommending an increase in the frequency of AAMI chemical water analyses, as well as for performing blood aluminum analyses at least quarterly.
Background: Before the deleterious effects of aluminum accumulation on the course of treatment for patients in end stage renal disease was fully appreciated, aluminum-containing phosphate binders and anti-acid medications were widely used. With the recognition that aluminum strongly interferes with the two major endocrine treatment moieties, the therapeutic administration of erythropoietin and calcitriol, efforts have been directed toward minimizing patient exposure to this potentially toxic substance. Thus, calcium-based phosphate binders have widely replaced aluminum gels in many dialysis centers.
Many dialysis professionals have therefore reached the conclusion that aluminum analyses can be omitted or at least de-emphasized, since in the current era of effective water purification systems what was believed to be the previous major residual source of exposure to aluminum, the phosphate binders, no longer carries this danger.
I believe this view to be seriously mistaken, because (1) aluminum binders are not now and perhaps never were the major source of aluminum exposure; and (2) removing aluminum from the armamentarium of laboratory testing deprives the physician of a multi-faceted and very valuable analytical parameter.
Just as dialysis nephrologists can see in their everyday work aspects of patient care which is by nature hidden from remote-sited laboratory professionals, so too are the latter in a unique position to observe facets of the dialysis treatment process which cannot be seen by individual nephrologists. In particular, laboratory professionals are able to observe test values from many different dialysis centers simultaneously, and to draw conclusions which might not be evident to an individual nephrologist reviewing laboratory results only from one or a few related centers.
Aluminum is the most abundant metal on the earth's crust, accounting for about 7% of its weight. It is also the third most abundant element after oxygen and silicon, with both of which it is usually found combined in nature. These alumino-silicates form much of the material of clays and other common minerals. As such, aluminum compounds form a very common component of dusts, so that aluminum contamination constitutes an ever-present danger to many processes which must be kept free of the metal (such as collection of specimens for aluminum analysis).
Case 1:
Table 1 shows a set of results of serum aluminum analyses all performed on the same day, excerpted from an actual work list in our laboratory:
What inference can we draw from this data? In the first place, it is evident that Center B has an aluminum problem, because analytical problems are excluded by the facts that (1) all centers have been supplied with the same aluminum-free tubes, and (2) Center B is the only one in this day's run in which there is a center-wide elevation of blood aluminum values. Now it seems highly unlikely that all or most of the patients in any one center would suddenly and inexplicably begin to ingest aluminum-containing medications. That leaves as a strong probability only that there is a center-wide water problem which was previously undetected.
Investigation showed that in this case the local water authority, in response to recent drought conditions, was adding excessive amounts of alum (potassium aluminum sulfate) to the water supply to precipitate particulate matter. This is a venerable and standard procedure for water purification1 which antedates the advent of dialysis by many decades, and continues, unfortunately, in widespread use. In this particular case the incoming water had an aluminum content of 0.3 ppm, too high for the center RO system to bring the product water within the AAMI standard level2 (0.010 ppm). Since no AAMI water analysis had been performed for several months, and since no prior notification by the water authority was given, the water problem had already proceeded to the point of elevation of patient blood aluminum levels.
To categorize this case, the blood aluminum analyses were acting as a late warning indicator of a center water contamination problem. This is the worst possible way in which to discover such a problem, but it a step better than not to discover it at all.
An much more appropriate early warning program would have been to perform frequent AAMI chemical analyses on the water used to make dialysis fluid. However, the annual AAMI recommendation for water analysis2, if strictly followed, would allow discovery of this type of problem at any one time only by coincidence. The twelve months between analyses could theoretically be a period of silent aluminum accu-mulation which might be uncovered only by, e.g., quarterly patient blood aluminum analyses.
Case 2:
The specific problem with Center B seen in Table 1 suggests that the problem was incipient or at least of only moderate degree. However, this type of pattern can also present itself in a much more extreme way. Table 2 shows a similar excerpt from an aluminum work list done on a completely different month and date.
Lest it be thought that such occurrences are rare, in only my own experience as a dialysis laboratory director instances of a center-wide high patient aluminum have occurred on at least nine separate and distinct occasions. The aggregate number of dialysis patients affected totaled several thousand, and involved not only medical problems but potential legal ones as well.
Some of the primary causes of these events proved to be the following:
(a) Alum dumping into the water supply; apparently common under local conditions both of drought and flooding. This was the most frequent cause.
(b) Failure to monitor the RO rejection ratio when a membrane had torn.
(c) Failure to keep the pre-RO water softener reservoir filled with salt; when consequently insoluble salts (e.g., CaCO3) precipitate within the membrane, their sharp crystalline edges can micro-puncture the RO membrane. Again, this was also com-pounded by failure to monitor the RO output purity.
(d) Failure to turn the RO system back on after servicing, coupled with monitoring failure.
(e) The presence of some aluminum-containing component or contaminant within the dialysis system tubing; when this was finally changed, the problem rapidly receded.
The type of water system failure seen in (b), (c), and (d) requires some addi-tional comment. Since the contaminants which were allowed to pass into the dialysis fluid were not confined only to aluminum, the toxicity of other such substances must be considered. Although aluminum in the amounts likely to be encountered from water contamination is slowly, chronically, and increasingly toxic, it is not an immediate mortality risk. The same, however, cannot be said for fluoride, which can indeed cause acute mortality.
The amount of fluoride added by water authorities to the water supply is 1ppm, or five times the AAMI limit2 for dialysis water. More importantly, dialysis patients per treatment are exposed to at least 25 times the water volume ingested by normal adults, exposing the former to rapidly toxic levels of fluoride (potentially >100 mg) if the dialysis water has not been properly purified. Again, in cases like (b), (c), and (d), blood aluminum analyses were acting as a late warning system for all the water contaminants, and not just aluminum. Of course, this could only be true as long as the water has a high enough level of aluminum to affect the blood aluminum levels.
Case 3:
It is also perfectly possible for an isolated individual patient to show an unexpected elevated aluminum value. Table 3 illustrates two such events seen in a small section of the work list on a completely different day's run.
In the interests of brevity the rather large number of essentially normal values simultaneously obtained on patients from each of the centers listed are not included in the table, but the elevated values for the patients in centers O and Q were confined only to those patients.
Events of this type often require some medical detective work to determine the exact source of the exogenous aluminum. For the sample from Center O, the elevated value is consistent with aluminum medication ingestion, but the level for the Center Q patient was probably too high to make this a probable explanation. In point of fact, the source of the aluminum in this patient had not been clearly uncovered at the time of this writing, but the elevation persisted for many weeks and was being successfully treated by dialysis and desferrioxamine therapy.
Such individual elevated patient aluminum values are much more common than the center-wide events. In our laboratory one or more of them occur almost daily, and each requires analysis by center personnel to determine a possible cause and cor-rection, and by the laboratory as well to infer whether it is part of a center-wide pattern.
The implication of what has been said above is to underline the critical import-ance both of frequent AAMI chemical water analyses and at least of quarterly blood aluminum analyses. I believe that the AAMI recommendation for annual chemical water analyses2 is out of touch with the reality of actual experience. If these analyses were done monthly, they could do a much more creditable job of providing an early warning of impending feed-water, RO system, or dialysis system problems.
Modern technology is now certainly able to provide 24-hour turnaround both of total AAMI analyses at a moderate price of and patient blood aluminum analyses, with little or no danger of contamination from ambient aluminum-containing dusts. The era of waiting for days or weeks for either of these types of results should be long gone, and with them should also disappear objections to having these tests performed frequently because of delays in getting results from the laboratory3.
References and Footnote:
1. Budavari S (ed): The Merck Index, Twelfth ed., Merck & Co., Whitehouse Station, NJ, 1996. 377 (373).
2. Association for the Advancement of Medical Instrumentation. Hemodialysis Systems. 2nd ed. ANSI/AAMI RD5-1992. Arlington,VA: AAMI, 1993. American National Standard.
3. The author wishes to acknowledge the skilled and dedicated technical expertise of Mr. Tom Hendrix in the performance both of patient aluminum determinations and AAMI water analyses.
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