Increased body aluminum. An independent risk factor in patients undergoing long-term hemodialysis?

The clinical course and aluminum status of 38 patients who had been receiving dialysis for at least eight years and were still undergoing dialysis in 1985 were evaluated. Twenty-nine had evidence of increased aluminum burden, although only three had evidence of overt aluminum toxicity, and nine did not have evidence of increased aluminum burden. The patients in both the high- and low-aluminum group were similar with regard to age, the cause of their renal failure, presence of hypertension or coronary artery disease, previous parathyroidectomy, and a number of biochemical parameters, along with the amount of prescribed aluminum. All patients were followed up for the next two years or until they died. The amount of ingested aluminum was reduced, and in selected patients, treatment with intermittent infusions of deferoxamine mesylate was instituted. There were no deaths in the low-aluminum group, but ten of 29 died in the high-aluminum group: seven of vascular disease and three of infection. In addition, morbidity as defined by hospitalization for coronary or cerebral vascular disease or infection occurred in only two of the nine patients in the low-aluminum group and in 19 of the 29 patients in the high-aluminum group. These observations imply that the occurrence of increased body aluminum, as suggested by aluminum blood levels or by results of bone biopsies in some patients, has an adverse effect on morbidity and mortality and should be considered as a possible independent risk factor in patients who are receiving long-term hemodialysis.

The effect of diuretics on components of the urinary kallikrein-kininogen-kinin system in man.

The effects of acute infusions of diuretics on components of the human urinary kallikrein-kininogen-kinin system were determined. Normal human subjects were given infusions of chlorothiazide and furosemide in doses calculated to produce a comparable natriuresis and diuresis. Alterations in urine electrolyte excretion, kinins, total and intact kininogen, and total active kallikrein were determined before and after the diuretic administration. Chlorothiazide caused a significant increase in total, but not active, kallikrein and had no effect on kinins and total or intact kininogen. Furosemide did not alter total or active kallikrein, or intact kininogen, but did decrease kinin and total kininogen excretion significantly. These differences in effects were not related to urinary sodium excretion or urinary flow because both diuretics produced comparable effects on these parameters. We conclude that acute infusions of diuretics do not activate the kallikrein-kininogen-kinin system and that some of the previously described effects of diuretics on this system may be related to their site of action.

Plasma aluminum levels (unstimulated and stimulated): clinical and biochemical findings in 185 patients undergoing chronic hemodialysis for 4 to 95 months.

Plasma aluminum levels (unstimulated and stimulated by deferoxamine infusion), along with signs and symptoms associated with aluminum overload, were evaluated in 185 patients (97 men, 88 women; mean age, 58 +/- 8 years) who had been undergoing dialysis for 4 to 95 months and who were still receiving treatment in 1985 at a free-standing dialysis facility which has always used water purified by reverse osmosis. Monthly water aluminum levels never exceeded 15 micrograms/L; therefore, the major source of aluminum in these patients was oral phosphate binders. Unstimulated plasma aluminum levels ranged from 7 to 392 micrograms/L, averaged 81.5 +/- 56.4, and did not correlate with the duration of dialysis (r = 0.07; P greater than 0.31) or frequency of symptoms. Stimulated plasma aluminum levels increased in a linear fashion (r = 0.57; P less than 0.0001) with time on dialysis; however, there was no statistical association between the stimulated aluminum levels and a variety of nonspecific musculoskeletal or CNS symptoms, evidence of hyperparathyroidism, hematocrit, or calcium or phosphorus levels. These findings suggest that total body aluminum, as reflected in deferoxamine-stimulated serum aluminum levels, increases as a function of time undergoing dialysis.