M. K. Ward

FRACTURING DIALYSIS OSTEODYSTROPHY AND DIALYSIS ENCEPHALOPATHY: An Epidemiological Survey

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.

Outcome in patients on continuous ambulatory peritoneal dialysis and haemodialysis: 4-year analysis of a prospective multicentre study

In a study in seven large renal units in England, the morbidity and mortality of all patients starting continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis during 1983-85 were monitored prospectively over a 4-year period and related to reasons for choice of therapy and potential risk factors. 610 new patients (median age 52 years, range 3-80 years) started CAPD; 16% had diabetes mellitus and 21% cerebrovascular or cardiovascular disease. 329 patients (median age 48 years, range 5-77 years) started haemodialysis; 7% had diabetes mellitus and 17% cerebrovascular or cardiovascular disease. The Kaplan-Meier patient survival estimates at 4 years were 74% for haemodialysis and 62% for CAPD; technique survival figures for the same period were 91% for haemodialysis and 61% for CAPD. Coxs proportional hazards regression analysis showed that cerebrovascular/cardiovascular disease, age over 60 years, and diabetes mellitus were important predictors for survival in CAPD patients; there were no risk factors associated with permanent change to haemodialysis. In the haemodialysis group early change to CAPD was associated with presence of cerebrovascular or cardiovascular disease. The major cause of drop-out in both groups was transplantation. The mean length of hospital admission was 14.8 days per patient-year for CAPD and 12.4 days per patient-year for haemodialysis.

BRAIN-ALUMINIUM CONCENTRATION IN DIALYSIS ENCEPHALOPATHY

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.

A method for the routine determination of aluminium in serum and water by flameless atomic absorption spectrometry

A simple but reliable method for the routine determination of aluminium in serum and water by flameless atomic absorption spectrometry is described. No preparatory procedures are required for water samples, although serum is mixed with a wetting agent (Triton X-100) to allow complete combustion of the samples and to improve analytical precision. Precautions to prevent contamination during sample handling are discussed and instrumental parameters are defined. The method has a sensitivity of 35.5 pg and detection limits of 2.3 micrograms Al/l for serum and 1.3 micrograms Al/l for water. The method was used to determine the aluminium concentration in serum of 46 normal subjects. The mean aluminium content was 7.3 micrograms/l (range 2--15 micrograms/l.

ABSENCE OF A THERAPEUTIC EFFECT OF ZINC IN THE SEXUAL DYSFUNCTION OF HÆMODIALYSED PATIENTS

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.

Determination of serum ionised calcium by ion-exchange electrode in normal subjects

Serum ionised calcium concentration [Ca2+] was measured with a calcium selective electrode in 65 normal people. A mean value of 1.06 mmol/l (+/- 0.04 S.D.) with an actual range of 0.97 to 1.13 mmol/l was obtained. Serum samples refrigerated at 4 degrees C for 24 h were satisfactory for analysis. Storage of whole blood samples for 6 h at room temperature before separation caused a very small error (+0.04 mmol/l). Mean results and ranges were similar in males and females and there was no significant correlation with age. No significant change in serum [Ca2+] was found following a normal meal. Serum [Ca2+] and total serum calcium showed a very slight correlation (r = 0.35). The method is reproducible and sensitive.

ALUMINIUM TOXICITY IN RENAL FAILURE

There is now no doubt that aluminium contamination of water supplies used for the preparation of dialysis fluid can lead to encephalopathy, vitamin D resistant fracturing osteomalacia and microcytic anaemia in patients receiving haemodialysis. Although the introduction of adequate water treatment to remove aluminium has effectively stopped the epidemics of these diseases which made them the major cause of death in some dialysis units in the 1970’s, sporadic occurrences of identical syndromes have also been described in patients who have never received dialysis, have been trated exclusively with peritoneal dialysis or have received haemodialysis using water known to have a very low aluminium content. In these patients other sources of aluminium have been implicated, the oral administration of aluminium salts used as phosphate-binding agents and contamination of parenteral fluids being the culprits. The rate of aluminium accummulation, which has marked effects on the distribution within the body, has been slower with oral administration. Thus, a new pattern of aluminium-related disease with a different epidemiology is emerging in patients with renal failure. This has ensured that the prevention, detection and treatment of aluminium toxicity will continue to be an important part of nephrological practice for many years.

Multi-center Study on the Outcome of Patients on CAPD and Hemodialysis

Seven renal units in England entered 361 patients into a multicenter study of CAPD. After one year 92 patients on CAPD were compared to 42 on hemodialysis. CAPD was preferentially used for patients with diabetes mellitus or cardiac problems. Actuarial patient survival and technique survival did not differ with the two treatments. The hospitalization rate for vascular access problems complicating hemodialysis therapy was nearly as high as that for peritonitis and catheter problems in CAPD patients. The peritonitis rate was 2.4 episodes/patient yr.

Glycerol Instead of Dextrose As an Osmotic Agent in CAPD

Glycerol replaced dextrose as the osmotic agent in dialysis fluid for six patients undergoing CAPD. This resulted in lower plasma glucose concentrations and insulin levels. No toxicity was detected from glycerol absorption, even in one patient so exposed for 6 months. On a molar basis, however, glycerol induced less ultrafiltration than dextrose did. Because of the lower dialysate volume, clearances were less with glycerol than with dextrose.

Sexual Dysfunction in Patients Treated by CAPD

A comparison of sexual function in 27 male CAPD patients with that of 73 male hemodialysis patients revealed impotence in more than half of each group and testicular atrophy in the vast majority. Gynecomastia was infrequent. Plasma testosterone levels were higher in the CAPD population but differences in prolactin, FSH, TH and PTH were minor. The similarities in sexual function of hemodialysis and CAPD patients do not support middle molecule toxicity as a major pathogenetic factor in uremic sexual dysfunction.