A fatal case of aluminium encephalopathy in a patient with severe chronic renal failure not on dialysis

Sir,

Aluminum (Al) toxicity in patients with end-stage renal disease is a well known adverse effect due to either dialysate Al contamination or oral intake of Al-containing phosphate binders [1]. At present, the clinical forms of Al toxicity have almost disappeared. Al-containing drugs are given mainly as antacid agents and are often used without special caution in patients with chronic renal failure (CRF) not yet on dialysis. Herein, we report a case of fatal Al-related encephalopathy in a patient with severe CRF, not on dialysis, due to the intake of large doses of antacids containing Al for at least 3 years.

Case. A 59-year-old white male patient with CRF due to diabetic nephropathy was followed as an out-patient in our chronic kidney disease clinic. When he was 47 years old, diabetes mellitus was diagnosed, and he was treated with oral antidiabetics for 2 years and thereafter with insulin. At 55, a severe polyneuropathy and distal occlusive arterial disease with foot gangrene occurred that required the amputation of the left foot. He suffered from gastric pain which he self-treated with Al hydroxide (Maalox® TC). A gastroduodenoscopy was performed that revealed antral gastritis positive for Helicobacter pylori. Despite the antibiotic treatment, the patient continued taking Al hydroxide. From the age of 57, he regularly attended our chronic kidney disease clinic. His serum creatinine was between 3 and 4 mg/dl and his BUN between 75 and 85 mg/dl. At the age of 59, during a visit, the nephrologists noticed speech disturbances, mostly stuttering. A cerebral computed tomography (CT) scan was performed, which was normal. He had a hypochromic anaemia (Hb = 9.2 mg/dl, MCV = 65 fl), severe CRF (creatinine = 5.4 mg/dl), hyperkalaemia (6 mEq/l) and a normal serum Ca (4.7 mEq/l). Haemodialysis was started. On admission, the patient appeared malnourished. The neurological examination showed disorientation, spontaneous tremor and no sign of meningeal irritation. All other neurological tests were within normal limits. After a few dialysis sessions, the patient became confused and lethargic. The CT scan was repeated, but it was again unremarkable. The electroencephalogram showed wide {theta} and {theta}-{delta} waves, often in a triphasic fashion, and diffuse slow spikes. Serum Al was checked and found to be 740 µg/l. After a dialysis session, the patient fell and fractured a femur. He was treated with 500 mg of desferrioxamine/day intramuscularly (Novartis, Origgio, Italy) in 250 ml of physiological solution daily, for 1 month until death, but the neurological disturbances progressed steadily. Repeated general seizures occurred, and the patient died of a cardiogenic shock during a general convulsion.

At autopsy, the brain weighed 1280 g, it was slightly atrophic and no focal lesions were found. On light microscopicy, the grey matter presented spongiosis, cortical gliosis and neuronal atrophy. Slight gliosis was present in the basal nuclei; neuronal thickening was observed in the pons. Silver staining of paraffin slides revealed argyrophilic deposits in epithelia of choroid plexus, the cytoplasm of glial cells and different neuronal populations of brainstem, cortex and subcortical grey matter. Al concentrations (µg/g fresh tissue) were 2.46 in the frontal lobe, 3.56 in the parietal lobe, 2.34 in the temporal lobe, 2.89 in the cerebellum, 15.5 in the kidney, 20.3 in bone and 6.5 in the heart.

Comment. This case showed all three syndromes related to Al toxicity, namely encephalopathy, bone disease and microcytic anaemia. The total amount of ingested aluminum was at least 3 kg in 3 years. He did not have end-stage renal disease when he started taking Al hydroxide, but moderate to severe renal failure with a serum creatinine between 3 and 4 mg/dl.

Most reported cases refer to patients on peritoneal dialysis or haemodialysis. Only a few have been described in patients not yet on dialysis: a patient who developed Al-related bone disease after the ingestion of 711 g in 1 year [2]; a child with microcytosis due to high Al doses given to treat hyperphosphataemia [3]; and two patients with dialysis encephalopathy syndrome due in one case to the use of Al-containing phosphate binders for 2 years, and in the other to the concommitant intake of citrate [4]. Four other CRF patients took Al hydroxide and citrate together and developed encephalopathy [5]. Finally, a case of osteomalacia due to prolonged antacid use was reported in a patient with normal renal function [6].

The peculiarity of the present case is the presence of the complete picture of Al toxicity and the exceedingly high levels of serum Al.

The kinetics of Al absorption in CRF were well described by Sárszegi et al. [7]. In patients with moderate CRF, serum Al concentration was twice as high as baseline, even 24 h after the administration of a compound containing 58.1 mg of Al. The most interesting finding was that CRF patients were unable to excrete Al as compared with healthy subjects, i.e. the problem was not absorption, but excretion. Moreover, Al kinetics were the same in patients with moderate and severe CRF.

Although sufficient evidence exists to show that some degree of Al overload occurs in Al-treated patients even in the presence of normal renal function, the problem arises with long-term treatments with Al-containing compounds. This was the case in our patient and in the other patients alluded to above [2–6]. The occurrence of Al intoxication is so rare at present that it no longer seems to be a problem. However, because we do not know the prevalence of the use of Al compounds in CRF patients, the symptoms of mild forms of intoxication may be easily missed. As a matter of fact, the cases described in the literature are very severe. Not much is known about the effects of low-dose long-term exposure, or whether it may contribute to patient morbidity and mortality in the long run.

It is well known that Al-containing compounds should be avoided in CRF patients, that care should be taken in limiting their use to the short-term reduction of high serum phosphate, and that all possible alternatives should be considered. However, sometimes, as in our case, the patient self-prescribes the drug. In this situation, only regular monitoring can detect patients at risk of Al intoxication.

Conflict of interest statement. None declared.

Paolo Zatta1, Pamela Zambenedetti2, Erich Reusche3, Florian Stellmacher3, Alberto Cester4, Paolo Albanese4, Gina Meneghel5 and Maurizio Nordio6

1 CNR-Institute for Biomedical Technologies Metalloproteins Unit Department of Biology University of Padova Vialle G. Colombo 3 35121 Padova2 Pathology Division and Brain Bank4 Geriatric Division5 Nephrology and Dialysis Unit General Hospital ULS 513 Dolo-Venice6 Nephrology and Dialysis Unit SS Giovanni e Paolo Hospital ULSS 12, Venezia, Italy3 Institute for Pathology/Neuropathology Medical School Luebeck, Germany Email: zatta{at}mail.bio.unipd.it

References

  1. Wills MR, Savory J. Aluminum and chronic renal failure: sources, absorption, transport, and toxicity. Crit Rev Clin Lab Sci 1989; 27: 59–107[ISI][Medline]
  2. Kaye M. Oral aluminum toxicity in a non-dialyzed patient with renal failure. Clin Nephrol 1983; 20: 208–211[ISI][Medline]
  3. Shah NR, Oberkircher OR, Lobel JS. Aluminium-induced microcytosis in a child with moderate renal insufficiency. Am J Pediatr Hematol Oncol 1990; 12: 77–79[ISI][Medline]
  4. Russo LS, Beale G, Sandroni S, Ballinger WE. Aluminium intoxication in undialysed adults with chronic renal failure. J Neurol Neurosurg Psychiatry 1992; 55: 697–700[Abstract]
  5. Woodson GC. An interesting case of osteomalacia due to antacid use associated with stainable bone aluminium in a patient with normal renal function. Bone 1998; 22: 695–698[CrossRef][ISI][Medline]
  6. Bakir AA, Hryhorczuk DO, Ahmed S et al. Hyperaluminemia in renal failure: the influence of age and citrate intake. Clin Nephrol 1989; 31: 40–44[ISI][Medline]
  7. Sárszegi Z, Nagy J, Jobst K. The kinetics of initial gastrointestinal absorption of an aluminium-containing antacid (Tisacid) in patients with various stages of chronic renal insufficiency. Nephrol Dial Transplant 1997; 12: 372–373[Free Full Text]




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