Study of anemia after late introduction of everolimus in the immunosuppressive treatment of renal transplant patients.
BACKGROUND
mTOR inhibitors (imTOR) are immunosuppressive drugs that have a concentration-related effects on hematopoiesis, potentially resulting in anemia. The reason is uncertain, but a pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we studied whether everolimus influenced iron homeostasis.


METHODS
We studied iron homeostasis in 43 patients after late introduction of everolimus into the immunosuppressive treatment. Thirty-seven patients (86%) were receiving mycophenolate. Hemoglobin concentration, red blood cell count, mean corpuscular volume, serum iron, ferritin, C-reactive protein levels, and transferrin saturation were evaluated 3 months before and 1, 3, and 6 months after the switch.


RESULTS
The percentage of anemic patients preconversion was 18.6% and it was 34.9% at 3 months and 18.6% at 6 months. We did not observe a significant reduction in hemoglobin, but there was increased red blood cell count after everolimus introduction, with a significant reduction in mean corpuscular volume. Serum iron and transferrin saturation levels were also markedly reduced after the switch, while ferritin serum concentrations remained stable. An improvement in renal function was observed.


CONCLUSIONS
The anemia caused by everolimus--microcytosis, low serum iron, despite high ferritinemia, and elevated C-reactive protein levels--was consistent with the anemia of a chronic inflammatory state. This alteration occurred within the first months postconversion and disappeared at 6 months. The combination of mycophenolate and everolimus seemed to be useful without significant secondary effects.
Sánchez Fructuoso
A
A
Nephrology Department, Hospital Clinico San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
Calvo
N
N
Moreno
M A
MA
Giorgi
M
M
Barrientos
A
A
D000740:Anemia / Q000453:epidemiology* / Q000517:prevention & control; D002097:C-Reactive Protein / Q000378:metabolism; D000068256:Darbepoetin alfa; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068338:Everolimus; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007501:Iron / Q000097:blood / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D011183:Postoperative Complications / Q000453:epidemiology; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D014168:Transferrin / Q000378:metabolism
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D014168:Transferrin; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D002097:C-Reactive Protein; D005293:Ferritins; D000068338:Everolimus; D007501:Iron; D020123:Sirolimus