Reduced-exposure cyclosporine is safe and efficacious in de novo renal transplant recipients treated with enteric-coated mycophenolic acid and basiliximab.
BACKGROUND
The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab.


METHODS
A 12-month, multicenter, randomized, open-label trial was carried out in which de novo renal transplant patients received enteric-coated mycophenolate sodium, cyclosporine microemulsion, steroids and basiliximab. Patients were randomized to receive standard-exposure (n = 45) or reduced-exposure (n = 44) cyclosporine, based on differing C2 target ranges, after the first month post-transplant.


RESULTS
Cyclosporine exposure gradually increased over the first month and was lower than previously recommended. Mean calculated creatinine clearance (primary end-point) was similar in the standard-exposure and reduced-exposure groups at month 6 (55.3+/-3.2 ml/min and 61.5+/-3.7 ml/min respectively, n.s.). There were 4 deaths but no death-censored graft losses, resulting in 95.5% patient and graft survival at one year in both groups. At 6 and 12 months, the incidence of biopsy-proven acute rejection was 17.8% and 17.8% in the standard-exposure group, and 13.6% and 15.9% in the reduced-exposure group. Adverse events were similar between treatment groups. Exploratory analyses could not identify a lower limit for the optimal CsA exposure range, but results suggested that high exposure at one year was associated with deteriorating renal function.


CONCLUSIONS
These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine, steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients. Lower C2 targets than previously recommended, particularly early post-transplant, do not appear to be associated with compromised efficacy.
Budde
K
K
Department of Nephrology, Campus Charité Mitte Charité, Universitätsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany. klemens.budde@charite.de
Bosmans
J L
JL
Sennesael
J
J
Zeier
M
M
Pisarski
P
P
Schütz
M
M
Fischer
W
W
Neumayer
H H
HH
Glander
P
P
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D000077552:Basiliximab; D001530:Belgium / Q000453:epidemiology; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004655:Emulsions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006084:Graft Rejection / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D015996:Survival Rate; D013608:Tablets, Enteric-Coated; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D004655:Emulsions; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D000077552:Basiliximab; D003404:Creatinine; D009173:Mycophenolic Acid