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

BACKGROUND: According to the recommendations proposed at The Consensus Conferenceon Diagnosis and Treatment of Aluminium Overload in End-StageRenal Failure Patients, Paris, 1992 low-dose desferrioxamine(DFO) treatment was applied for the first time in 41 acutelyaluminium-intoxicated patients. METHODS AND RESULTS: DFO-related neurological/ophthalmological side-effects wereobserved in nine of 11 patients with a post-DFO serum aluminiumlevel >300 µg/litre and in two patients of 30 belowthis level after a single administration of a 5-mg/kg dose ofthe chelator in the conventional way (i.e. the last hour ofa dialysis session). They were no longer observed after introducingan alternative DFO administration schedule (i.e. administrationof the chelator 5 h prior to the start of a haemodialysis session;group I: n=14). A significant decrease in the serum aluminiumlevels as well as in the post-DFO serum aluminium increment(sAl) was observed during the first 6 months' course of low-doseDFO treatment in group I as well as group II (which consistedof patients receiving DFO in the conventional way; n=27). Low-doseDFO treatment was accompanied by a significant increase in themean ±SD serum iPTH levels (group I: 174±245 upto 286±285 ng/litre; group II: 206±272 up to 409±424ng/litre; P<0.005) and the mean corpuscular volume (groupI: 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 ferritinlevels significantly decreased in both groups. No further side-effectswere observed during the DFO course. Patients in which DFO treatmentcould be stopped (i.e. subjects in which both serum aluminiumand sAl were below 50 µg/litre at two successive occasions)before the end of the 6-months' treatment course had a significantlygreate residual diuresis (700±682 ml/min vs 84±109ml/24 h). Also, residual diuresis was found to protect againstaluminium intoxication as reflected by the values noted in groupI versus those in group II. CONCLUSIONS: The 5-mg/kg DFO treatment provides a safe and adequate therapyfor aluminium overload. In severely aluminium-intoxicated patientspresenting post-DFO serum aluminium levels above 300 µg/litreDFO should be given once weekly 5 h prior to high-extractiondialysis ensuring (i) maximal chelation of aluminium (ii) limitedexposure to circulating aluminoxamine levels, and (iii) adequateremoval of the latter compound. Finally, the necessity for abetter communication between the local water distribution companiesand the dialysis centres is a major lesson that can be drawnfrom this dramatic intoxication.