The aluminum content of muscle, bone and brain was measured in control subjects and in uremic patients on dialysis who had been maintained on phosphate-binding aluminum gels. The mean musc...

https://www.nejm.org/doi/pdf/10.1056/NEJM197601222940402?listPDF=true

The dialysis encephalopathy syndrome. Possible aluminum intoxication.

Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

/pdf/human-health-risk-assessment-for-aluminium-aluminium-oxide-5dfetd69xm.pdf

Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Renal osteodystrophy

Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind.

Metabolism and possible health effects of aluminum.

Osteomalacic dialysis osteodystrophy: Evidence for a water-borne aetiological agent, probably aluminium.

1. Eight patients with chronic renal failure (creatinine clearance 4·9–22·0 ml/min) were given 75–150 ml of aluminium hydroxide gel (‘Aludrox’) daily for 20–32 days. 2. In all patients there was a decrease in plasma phosphorus. The phosphorus balance became more negative in four and less positive in one, remained unchanged in two, and became positive in one. 3. Patients absorbed 100–568 mg of aluminium daily. In two of three patients the content of aluminium in the iliac bone increased but not above normal values. 4. The concentration of parathyroid hormone was decreased by aluminium hydroxide therapy in three patients in whom there was an increase in plasma calcium and in one other patient in whom plasma calcium did not change.

The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances, the serum parathyroid hormone concentration and the aluminium content of bone in patients with chronic renal failure.

The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances and the plasma parathyroid hormone in patients with chronic renal failure.

W. V. Hynson

Papers

The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances, the serum parathyroid hormone concentration and the aluminium content of bone in patients with chronic renal failure.

The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances and the plasma parathyroid hormone in patients with chronic renal failure.