Erythropoietin, aluminium, and anaemia in patients on haemodialysis.
Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.
Rosenlöf
K
K
Fourth Department of Medicine, Helsinki University Central Hospital, Finland.
Fyhrquist
F
F
Tenhunen
R
R
D000328:Adult; D000535:Aluminum / Q000009:adverse effects* / Q000097:blood; D000747:Anemia, Hypochromic / Q000097:blood / Q000139:chemically induced*; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use; D004341:Drug Evaluation; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004906:Erythrocyte Count / Q000187:drug effects; D004912:Erythrocytes / Q000737:chemistry / Q000201:enzymology*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005294:Ferrochelatase / Q000097:blood*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000097:blood; D008190:Lyases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011524:Protoporphyrins / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D006435:Renal Dialysis
D011524:Protoporphyrins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000535:Aluminum; D011163:Hydroxymethylbilane Synthase; D008190:Lyases; D005294:Ferrochelatase; D003676:Deferoxamine