Reduction in erythropoietin resistance after conversion from sirolimus to enteric coated mycophenolate sodium.
BACKGROUND
Anemia is a known adverse effect of sirolimus (SRL) therapy. Sirolimus may contribute to anemia by a direct antiproliferative effect or by increasing inflammation, worsening kidney function, or decreasing iron utilization. After observing the need for high dose exogenous erythropoietin dosage in some patients on SRL, we hypothesized that SRL therapy may influence anemia by inducing a state of erythropoietin resistance.


METHODS
Twenty-five stable renal transplant patients on maintenance tacrolimus and SRL therapy were enrolled in a prospective trial with conversion from SRL to enteric coated mycophenolate sodium. Measurement of plasma erythropoietin and red cell indices were performed pre- and postconversion.


RESULTS
Renal function remained unchanged after conversion. Serum hemoglobin (Hb) increased in 18/21 (86%) of patients after conversion. Endogenous erythropoietin level decreased from a median of 28.3 (11.5-374) to 16.6 (3.1-78.8) mIU/mL, (P<0.001); and the erythropoietin:Hb ratio dropped from 2.7 (0.7-34.3) to 1.2 (0.2-6.7), (P<0.001); indicating less erythropoietin resistance after conversion. Mean corpuscular volume increased after conversion, but transferrin saturation and ferritin did not change. Conversion was complicated by posttransplant erythrocytosis in two patients.


CONCLUSIONS
Conversion from SRL to enteric coated mycophenolate sodium led to an increase in Hb and a decrease in erythropoietin resistance in stable kidney transplant recipients. Increase in Hb seemed to be independent of renal functional changes or changes in iron sequestration.
Augustine
Joshua J
JJ
Division of Nephrology and Hypertension, Department of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA. joshua.augustine@uhhospitals.org
Rodriguez
Victoria
V
Padiyar
Aparna
A
Bodziak
Kenneth A
KA
Schulak
James A
JA
Hricik
Donald E
DE
D000740:Anemia / Q000139:chemically induced / Q000517:prevention & control; D004351:Drug Resistance; D004921:Erythropoietin / Q000172:deficiency*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; D004921:Erythropoietin; D009173:Mycophenolic Acid; D020123:Sirolimus