Replacement of mycophenolate acid with everolimus in patients who became neutropenic after renal transplant.
OBJECTIVE
Neutropenia after kidney transplant is an adverse event usually treated with a dosage reduction of mycophenolic acid. We evaluated the efficacy and safety of substituting mycophenolic acid with everolimus in patients with persistent neutropenia after kidney transplant.


METHODS
This study was a retrospective analysis. A total of 17 patients who were initially treated with mycophenolic acid (1912 ± 196 mg/d), calcineurin inhibitors, and methylprednisolone for kidney transplant were included.


RESULTS
In 15 patients, neutropenia occurred within the first 3 months (during valganciclovir administration), and in 2 patients between the fourth and sixth month after transplant. One hundred eighteen episodes of neutropenia were recorded, originally treated by reducing the dosage of mycophenolic acid (765 ± 390 mg/d) and administering granulocyte colony-stimulating factor. Three patients experienced acute rejection 5 to 10 days after reducing the dosage of mycophenolic acid, and they were successfully treated with pulse steroids. Five patients developed cytomegalovirus infection 108 ± 65 days after the onset of neutropenia. After replacing mycophenolic acid with everolimus, episodes of neutropenia were observed in 6 patients. In 1 patient, discontinuing everolimus was necessary after 1.5 months of treatment. In 5 patients with cytomegalovirus infection, neutropenia subsided after termination of valganciclovir treatment. In the remaining 11 patients, no episodes of neutropenia were observed. No episodes of acute rejection occurred, and renal function remained stable during a followup of 47 ± 30 months (estimated glomerular filtration rate [eGFRMDRD6]: 45 ± 14 mL/min/1.73 m2→47 ± 22 mL/min/1.73 m2].


CONCLUSIONS
Replacing mycophenolic acid with everolimus appears to be a safe and effective alternative treatment in neutropenic renal transplant recipients.
Transplantation Center, University Hospital, Patras, Greece.
Eirini
E
Savvidaki
Panagiotis
P
Kazakopoulos
Evangelos
E
Papachristou
Dimitrios
D
Karavias
Vasilios
V
Zavvos
Georgios
G
Voliotis
Pantelitsa
P
Kalliakmani
Markos
M
Marangos
Dimitrios S
DS
Goumenos
D000328:Adult; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects*; D009503:Neutropenia / Q000139:chemically induced*; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013256:Steroids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D000077562:Valganciclovir
D007166:Immunosuppressive Agents; D013256:Steroids; D000068338:Everolimus; D000077562:Valganciclovir; D009173:Mycophenolic Acid; D015774:Ganciclovir; D020123:Sirolimus