Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity

J. T. McCarthy, D. S. Milliner, W. J. Johnson

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Abstract

A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9 ± 11.2 mg/kg (mean ± SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373 ± 250.4 ng/ml. The increase in 20 aluminium-negative patients was 231 ± 179.2 ng/ml (p < 0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336 ± 442 μleq/ml) than aluminium-negative patients (1278 ± 1400 μleq/ml; p < 0.05). A change in serum aluminium level of >200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level <200 μleq/ml and a change in serum aluminium of >200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received long-term therapy (11.0 ± 4.3 months) with DFO at an average starting dose of 41.7 ± 17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5-7 months of treatment, serum aluminium levels decreased from 401 ± 262 ng/ml to 245 ± 217 ng/ml (p < 0.01); erythrocyte mean corpuscular volume increased from 86.3 ± 10.91 fl to 94.1 ± 9.23 fl (p < 0.02); and serum calcium decreased from 10.4 ± 0.94 mg/dl to 9.9 ± 0.70 mg/dl (p < 0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251 ± 229.8 μg/l to 45 ± 29.3 μg/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term DFO administration were hypotension (11 patients), gastrointestinal upset (seven patients), porphyria cutanea tarda-like lesions (three patients), and transient visual disturbance (one patient). There was a decrease in stainable bone aluminium in all nine patients with paired bone biopsy specimens (pre- and post-DFO). Seven of these nine patients had beneficial changes in bone histology; patients who had undergone total parathyroidectomy had no change. Our experience indicates that the DFO infusion test, in conjunction with immunoreactive parathyroid hormone levels, has some use in identifying dialysis patients with aluminium toxicity. In addition, long-term DFO therapy can be important in the treatment of patients with significant aluminium toxicity. The potentially serious reported side-effects of DFO therapy mean that it should only be used when symptoms demand treatment and when clinical monitoring for toxicity can be performed regularly.

Original languageEnglish (US)
Pages (from-to)257-276
Number of pages20
JournalQuarterly Journal of Medicine
Volume74
Issue number275
StatePublished - 1990

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McCarthy, J. T., Milliner, D. S., & Johnson, W. J. (1990). Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity. Quarterly Journal of Medicine, 74(275), 257-276.