Rapamycin in patients with chronic renal allograft dysfunction.
OBJECTIVE
Nephrotoxicity of calcineurin inhibitors (CNI) complicates the management of chronic renal allograft dysfunction. Rapamycin is a promising immunosuppressive agent free of nephrotoxicity. The effect of conversion from CNI to rapamycin in recipients with chronic allograft dysfunction is still unclear. We investigated the effect of rapamycin in patients with chronic allograft dysfunction.


METHODS
We conducted a prospective study on kidney transplant recipients with chronic allograft dysfunction. The patients were under classic CNI, mycophenolate mofetil, and prednisolone triple therapy. They had progressive deterioration of the allograft function. They were converted from CNI to rapamycin directly and observed for 6 months. The CNI serum levels before the conversion were within recommended range. Allograft function, clinical features and adverse effects were evaluated before and after the rapamycin conversion.


RESULTS
A total of 16 patients were enrolled. Six of them (37.5%) failed to have a smooth conversion because of deterioration of allograft function and intractable adverse effects. Ten patients (62.5%) went through the 6-month observation period with improved graft function. The average reduction of serum creatinine was 27.7% (p < 0.001) in successful conversion. There were no significant differences on age, gender, lipid profile, sugar control, and rapamycin levels between successful and failed conversion. Anemia and diastolic blood pressure were significantly improved after successful conversion. The failed patients had a longer transplantation period (6.1 +/- 4.1 vs. 11.2 +/- 3.4 yr, p < 0.05). Two of them (12.5%) developed bacteria pneumonia. Self-limited diarrhea developed in three patients (18.8%).


CONCLUSIONS
We suggested that conversion from CNI to rapamycin was beneficial in some kidney transplant recipients with chronic allograft dysfunction.
Wu
Mai-Szu
MS
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan. mazwu1@adm.cgmh.org.tw
Chang
Chiz-Tzung
CT
Hung
Cheng-Chieh
CC
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D065095:Calcineurin Inhibitors; D016022:Case-Control Studies; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use
D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D006454:Hemoglobins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D003404:Creatinine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus