Low-dose (5 mg/kg) desferrioxamine treatment in acutely aluminium-intoxicated haemodialysis patients using two drug administration schedules

Abstract

Background: According to the recommendations proposed at The Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure Patients, Paris, 1992 low-dose desferrioxamine (DFO) treatment was applied for the first time in 41 acutely aluminium-intoxicated patients.

Methods and results: DFO-related neurological/ophthalmological side-effects were observed in nine of 11 patients with a post-DFO serum aluminium level > 300 micrograms/litre and in two patients of 30 below this level after a single administration of a 5-mg/kg dose of the chelator in the conventional way (i.e. the last hour of a dialysis session). They were no longer observed after introducing an alternative DFO administration schedule (i.e. administration of the chelator 5 h prior to the start of a haemodialysis session; group I: n = 14). A significant decrease in the serum aluminium levels as well as in the post-DFO serum aluminium increment (delta s A1) was observed during the first 6 months, course of low-dose DFO treatment in group I as well as group II (which consisted of patients receiving DFO in the conventional way; n = 27). Low-dose DFO treatment was accompanied by a significant increase in the mean +/- SD serum iPTH levels (group I: 174 +/- 245 up to 286 +/- 285 ng/litre; group II: 206 +/- 272 up to 409 +/- 424 ng/litre; P < 0.005) and the mean corpuscular volume (group I: 80 +/- 6.4 up to 85 +/- 3.7 fL, P < 0.005; group II: 76 +/- 5.0 up to 87 +/- 4.3 fL, (P < 0.0001). Serum ferritin levels significantly decreased in both groups. No further side-effects were observed during the DFO course. Patients in which DFO treatment could be stopped (i.e. subjects in which both serum aluminium and delta sA1 were below 50 micrograms/litre at two successive occasions) before the end of the 6 months' treatment course had a significantly greater residual diuresis (700 +/- 682 ml/min vs 84 +/- 109 ml/24 h). Also, residual diuresis was found to protect against aluminium intoxication as reflected by the values noted in group I versus those in group II.

Conclusion: The 5-mg/kg DFO treatment provides a safe and adequate therapy for aluminium overload. In severely aluminium-intoxicated patients presenting post-DFO serum aluminium levels above 300 micrograms/litre DFO should be given once weekly 5 h prior to high-extraction dialysis ensuring (i) maximal chelation of aluminium (ii) limited exposure to circulating aluminium noxamine levels, and (iii) adequate removal of the latter compound. Finally, the necessity for a better communication between the local water distribution companies and the dialysis centres is a major lesson that can be drawn from this dramatic intoxication.