Excellent results with high-dose mizoribine combined with cyclosporine, corticosteroid, and basiliximab in renal transplant recipients: multicenter study in Japan.
We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 μg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve(0-9)). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.
Department of Renal Transplantation Center, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan. nkennishi3753@nifty.com
K
K
Nishimura
K
K
Uchida
K
K
Yuzawa
Y
Y
Fukuda
Y
Y
Ichikawa
K
K
Akioka
M
M
Fujisawa
A
A
Sugitani
S
S
Ito
T
T
Nakatani
T
T
Horimi
N
N
Yoshimura
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000627:therapeutic use; D001739:BK Virus / Q000472:pathogenicity; D000077552:Basiliximab; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; 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 / Q000493:pharmacokinetics; D007564:Japan; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000188:drug therapy / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D012263:Ribonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D012263:Ribonucleosides; C010052:mizoribine; D016572:Cyclosporine; D000077552:Basiliximab; D003404:Creatinine