From 7 of the 10 patients who died, serum samples had been collected during admission shortly (approx. 1 week) before death. Blood for AlS assay was also sampled from the 17 survivors, and sent by express mail to the LUMC Toxicology Laboratory in The Netherlands. All blood and serum were collected and stored in Al-free polypropylene and polystyrene tubes prerinsed with 1 M HNO3to avoid contamination.
Tissue samples (liver, bone, and cerebral cortex) were obtained at autopsy in Curaçao of four patients, under strict Al-free conditions. The instruments were thoroughly washed and rinsed with Al-free distilled water, and the (Al-containing) talcum was washed from the surgical gloves used when taking the samples. The samples were kept frozen at -20ºC during sto- rage and mailing to The Netherlands.
Al in serum was analyzed with electrothermal atomic absorption spectrometry (EAAS; Perkin-Elmer 3030; Perkin-Elmer, Nordwalk, CT, USA) with a transversal Zeeman background correction system, using a graphite furnace (HGA 600) and pyrolytically coated graphite tubes. A calibration range was
used between 0 and 200 µg/L; for standard solutions 20 and 100 µg/L the within-day precision was 13.8 and 6.1 %, and the between-day precision 22 and 8%. For levels > 200 µg/L, the calibration range was adapted between 200 and 1000 µg/L.4
Al in tissues was analyzed likewise, with a procedure developed earlier in this laboratory.5Tissue samples were digested in 1 mL of a mixture of 65% HNO3+ 96% H2SO4(4+1, v/v) and gradual heating to 105 ºC before EAAS
analysis.
Calcium and aluminum in tap water were determined by Spectra Laboratories (Fremont, CA, USA).
Results
The serum of 7 deceased patients, collected before death, contained a very high Al concentration: 808 ± 127 µg/L (mean ± S.E.M., n = 7, range 359 - 1275). In the survivors, this value was 255 ± 25 µg/L (mean ± S.E.M., n = 17, range 113 - 490), significantly lower than that of the non-survivors (P < 0.01). The results of the post-mortem analysis are presented in Table I, in which the tissue levels of Al are compared with the concentrations in serum obtained when the patients were still alive. In these serum samples, other ions were measured with standard clinical chemical methods. These ions were: Fe,
Mg, Ca, V, Si, Pb, and Hg, none of them being outside the normal range. It should be noted that at the time of blood collection for Al analysis the hypercalcaemia had been normalized.
Table 1. Post-mortem analysis of liver, bone and brain aluminum in four patients
Patient Serum (µg/L) Liver (µg/g) Bone (µg/g)a Cerebral cortex (µg/g)b A 517 43.0 21.9 1.09 B 696 32.7 88.7 1.40 C 1275 51.7 7.54 1.12 D 894 4.70 77.0 1.78 Reference values5,6,8 < 10 < 2 < 2 0.14 - 0.22 a
Collected from a femoral shaft b
From Table 1 it is clear that the Al concentrations in liver, bone and cerebral cortex are extremely high in comparison to the reference values which were taken from D’Haese et al.6and Van Ginkel et al.5
Analysis of tap water -sampled at the time of closure of the unit-showed a calcium concentration of 18.1 mg/L and an aluminum concentration of 650 µg/L. These concentrations, which are far too high for dialysate, were shown to be caused by release from the cement mortar with which a newly installed water piping system was lined.1
Discussion
The case history presented here confirms that exposure of dialysed patients to dialysate contaminated with Al may lead to systemic intoxication, as was reported as early as 1976.7 The sources of Al were either extracorporeal exposure to contaminated water, or high-dose oral aluminum hydroxide prescribed to bind dietary phosphate. Most cases of Al intoxication in dialysed patients that have been reported, however, are of the chronic type, showing a gradually developing cerebral impairment, starting with speech disturbances, motor apraxia, and twitching, slowly deteriorating into myoclonic jerks, seizures, and global dementia.8 Together with normochromic mycrocytic anaemia and Vitamin D-resistant osteomalacia, these symptoms of chronic Al intoxication in long-term dialysed patients are generally well-known to nephrologists involved in chronic intermittent haemodialysis. In this case, sudden exposure to an extremely high Al concentration in the dialysate took place, so that the normal onset of ‘dialysis encephalopathy’ was bypassed. In addition, the symptoms that were observed approximately 3 weeks after installation of the new water supply system were consistent with another well-known side effect of haemodialysis, the ‘hard water syndrome’. Hypercalcaemia was confirmed in all patients, and an extremely high calcium concentration in the tap water (17.2 mg/L, preferred value < 2 mg/L) provided an explanation for this diagnosis. These observations masked the underlying Al intoxication, which was suspected only after the hypercalcaemia was normali- zed without clinical improvement of the patients. Then, serum analysis showed very high AlS values in all patients. Analysis of the tap water at that time revealed an Al content of 650 µg/L, which should be below 10 µg/L.
Comparison of the serum levels of aluminum (AlS) from seven of the 10 deceased patients, collected ante mortem, with the AlS in the group survivors (n=17) indicates that the AlS level -which is generally accepted as an indicator for the total body burden of Al8- may have a predictive value for the outcome of Al poisoning.