Reversal of aluminium dialysis encephalopathy after desferrioxamine treatment.
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Biomedical subjects
Publications and source records attributed to M K Ward.
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When formalin-sterilized dialyzers were rinsed by our standard technique (similar to that used in many other dialysis centres) undesirable concentrations of formaldehyde were found in the dialyzers at the start of dialysis. When the technique was modified by passing part of the saline through the blood compartment immediately before connection and discarding the saline left in the dialyzer at the time of connection, the concentration of formaldehyde infused into the patient fell below 2 micrograms/ml. However, the dialyzers still contained up to 13 mg of formaldehyde which leached slowly from the dialyzer during simulated dialysis. Some residual formaldehyde was found in several components of the dialyzer but the great majority was contained in the cellulose membrane.
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Use of formalin to sterilize dialyzers is known to be responsible for the formation of anti-N-like antibody in long-term hemodialysis patients. Patients dialyzed as in-patients using formalin were found to be completely free of anti-N-like antibody, while among those on home dialysis, there was a high prevalence (31%) and incidence. The hospital patients were found to be receiving concentrations of formaldehyde less than 1 microgram/ml while those on home dialysis received 3-13 micrograms/ml. This is offered as an explanation for the absence of anti-N-antibody in patients using formalin-sterilized dialyzers.
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Over a two year period 15 patients on CAPD and 65 patients predominantly treated by haemodialysis received first grafts. There was no difference in graft survival in these two groups. In the continuous ambulatory peritoneal dialysis (CAPD) patients there were no post operative episodes of peritonitis, apart from one patient who had peritonitis at the time of transplantation. No technical difficulties were encountered at the time of grafting. CAPD is not a contraindication to transplantation.
Three cases of "sterile" peritonitis in CAPD patients are discussed, where the predominant white cell type in the peritoneal dialysis fluid was the eosinophil. No bacterial or fungal organism was isolated on repeated culture of the dialysis fluid and all had a benign course. The eosinophilic response appears to occur very soon after starting CAPD, is relatively asymptomatic and does not require antibiotic therapy. It is suggested that the eosinophilia is related to allergy to some constituent of the peritoneal dialysis system.
The effect of zinc therapy and placebo on sexual function and endocrine status was investigated in a double-blind study of 14 male patients with chronic renal failure on regular haemodialysis. Zinc chloride was added to the dialysate of 7 patients for 6 weeks, raising the serum zinc concentration by 17% and placebo was added to the dialysate of the other patients. At the start of the trial 9 patients said they had decreased sexual function. Records of penile erectile activity during sleep confirmed the organic nature of the sexual dysfunction. Plasma testosterone concentrations were low or in the low normal range, basal serum luteinising-hormone levels were raised, and the early luteinising-hormone response to luteinising-hormone-releasing hormone was exaggerated, suggesting primary testicular failure. Zinc administration had no significant effect on any aspect of sexual function assessed by questionnaire or nocturnal penile tumescence monitoring. Plasma testosterone and basal and stimulated gonadotrophin levels were also unaltered by zinc administration.
Thirty-two patients aged 8-63 years trained to manage themselves by continuous ambulatory peritoneal dialysis for end-stage renal failure achieved better steady-state serum biochemistry and much higher haemoglobin and lower serum phosphate concentrations than during treatment with haemodialysis up to one year before. Two patients, however, returned to intermittent haemodialysis because of recurrent peritonitis. Costs of the technique during the first year were less than half those incurred in the first year of home haemodialysis. Nevertheless, the major advantage was the ease with which patient independence and rehabilitation could be achieved. This technique is an appreciable advance over other forms of management for end-stage renal failure. Nevertheless, until it is more refined and long-term problems have been assessed it should probably be used only in established renal units where back-up treatments are available.
Results in 29 recipients of second renal transplants from cadaver donors show a significantly better graft survival at 1 year of 90% in 10 recipients who had not received blood transfusion before their first transplant compared to 41% in 19 recipients who had been transfused prior to their first transplant (P = 0.025).
A survey of 1293 patients in eighteen dialysis centres in Great Britain showed a highly significant rank correlation of the incidence of both fracturing dialysis osteodystrophy (osteomalacic dialysis osteodystrophy) and dialysis encephalopathy with the aluminium content of water used to prepare dialysate.
There is increasing evidence that aluminium accumulation in patients with impaired renal function has pathological consequences. The serum aluminium content of 45 patients with chronic renal failure was found to be significantly elevated when compared with normal subjects. A further rise in serum aluminium concentration was seen in patients with chronic renal failure when they were taking aluminium-containing phosphate binding agents. Patients with stable but moderately impaired renal function who are taking aluminium-containing phosphate binders for several years may be at risk from aluminium accumulation and the development of osteomalacia and encephalopathy as seen in patients on intermittent haemodialysis.
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Brain-aluminium concentrations were found to be significantly higher in 7 patients dying with dialysis encephalopathy (mean 15.9 microgram aluminium/g dry weight) than in 11 dialysed controls (4.4 microgram/g) and in 2 uraemic patients who were not dialysed (2.7 microgram/g). The grey matter from the patients with dialysis encephalopathy contained about three times as much aluminium as white matter. The results suggest that dialysis with untreated and/or softened tap-water (aluminium concentration 0.1-1.2 mg/1) makes the major contribution to brain-aluminium levels; dialysis with deionised water (aluminium concentration normally less than 0.02 mg/1) and intake of phosphate-binding AL(OH)3 gel are less important. Brain aluminium levels remain elevated for up to four years after restoration of good renal function by transplantation. The association of dialysis encephalopathy with high levels of aluminium in the brain and in the dialysis water emphasises the potential neurotoxicity of aluminium in man.