Loss of captopril-bound Fe by end-stage renal failure patients during hemodialysis.
BACKGROUND
Patients on chronic hemodialysis often suffer from severe anemia, the outcome of iron deficiency and inadequate response to erythropoietin. Antihypertensive treatment with captopril worsens anemia, erythropoietin production and iron balance in hemodialysis patients. We investigated the possibility that iron chelation by captopril in the blood may result in elimination of iron-captopril complexes during hemodialysis, thus minimizing the effect of both medications.


METHODS
Twelve hypertensive hemodialysis patients (group 1) were treated with 12.5 mg/day captopril, while their 12 counterparts received 1.25 mg/day ramipril. Following two weeks of treatment and two weeks of "washout", captopril in group 1 was substituted with ramipril and ramipril in group 2 was replaced by captopril for an additional two week period. Blood and dialysate samples were procured at the beginning and the end of the dialysis, for iron, aluminum, transferin, ferritin, hemoglobin (Hb) and hematocrit (Htc) determination.


RESULTS
Iron, ferritin, transferin, Hb and Htc were decreased in the captopril-treated group 1. They similarly decreased in group 2 following replacement of ramipril by captopril for an additional period of two weeks. Significant amounts of iron were detected in dialysates of captopril, but not ramipril-treated patients. At the end of the dialysis, iron content was further increased in dialysates of the captopril-treated groups.


CONCLUSIONS
1) Captopril-chelated iron is eliminated in dialysis fluid during the dialysis session, apparently contributing to captopril-related anemia in patients on chronic hemodialysis. 2) Antihypertensive treatment with angiotensin converting enzyme (ACE) inhibitors other than captopril might prove advantageous for this patient category.
Averbukh
Zhan
Z
Nephrology Division, Assaf Harofeh Medical Center, Zerifin, Israel.
Berman
Sylvia
S
Kishinevsky
Elena
E
Feldman
Leonid
L
Cohn
Mirel
M
Rapoport
Micha
M
Galperin
Elena
E
Dishi
Victor
V
Weissgarten
Joshua
J
D000740:Anemia / Q000097:blood / Q000209:etiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D002216:Captopril / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D005293:Ferritins / Q000097:blood; D006400:Hematocrit; D015312:Hemodialysis Solutions / Q000737:chemistry; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy; D017257:Ramipril / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D006435:Renal Dialysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015312:Hemodialysis Solutions; D006454:Hemoglobins; D007502:Iron Chelating Agents; D005293:Ferritins; D002216:Captopril; D007501:Iron; D017257:Ramipril