Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.
Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.
D000328:Adult; D000535:Aluminum / Q000097:blood*; D001708:Biopterins / Q000097:blood; D003676:Deferoxamine / Q000494:pharmacology; D004093:Dihydropteridine Reductase / Q000097:blood*; D004912:Erythrocytes / Q000201:enzymology*; D006801:Humans; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D006435:Renal Dialysis / Q000009:adverse effects*
D001708:Biopterins; D000535:Aluminum; D004093:Dihydropteridine Reductase; D009247:NADH, NADPH Oxidoreductases; D003676:Deferoxamine