Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab: a 12-month randomized trial in renal transplant recipients.
BACKGROUND
Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C(2)) has been shown to be the most reliable, single-point surrogate marker for AUC. The objective of this study was to measure renal function beyond month 2 post-transplant using two different C(2) maintenance targets in combination with enteric-coated mycophenolate sodium (EC-MPS), corticosteroids, and basiliximab induction.


METHODS
In this open-label, multicenter trial, renal transplant recipients entered one of two randomized groups at day 61 post-transplant: group A (higher-C(2) range) or group B (lower-C(2) range).


RESULTS
Patients (164) were recruited, and 141 patients were entered the randomized groups (group A, n = 66; group B, n = 75). At 12 months, the mean calculated creatinine clearance was significantly greater in group B than in group A (79.2 vs. 71.0 mL/min, p < 0.05). Biopsy-proven acute rejection occurred in 14.7% patients in group B and in 24.2% patients in group A (n.s.). During the 12-month trial, 17.7% patients discontinued EC-MPS because of adverse events. Group B (44.0%) had fewer serious adverse events when compared with group A (62.1%; p = 0.04). Overall patient and graft survival were 99.4% and 95.7% respectively. Among 99 high-risk patients (i.e., African-American race, previous transplant, PRA >35% or >4 HLA mismatches), mean creatinine clearance at 12 months was 65.6 mL/min and biopsy-proven rejection occurred in 20.2% patients.


CONCLUSIONS
Low cyclosporine C(2) levels are associated with improved renal function compared with higher C(2) levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C(2) levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.
Cibrik
Diane
D
Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA. dcibrik@umich.edu
Meier-Kriesche
Herwig-Ulf
HU
Bresnahan
Barbara
B
Wu
You Min
YM
Klintmalm
Goran
G
Kew
Clifton E
CE
Kuo
Paul C
PC
Whelchel
John
J
Cohen
David
D
Baliga
Prabakar
P
Akalin
Enver
E
Benedetti
Enrico
E
Wright
Francis
F
Lieberman
Bonnie
B
Ulbricht
Bettina
B
Jensik
Stephen
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019540:Area Under Curve; D000077552:Basiliximab; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009173:Mycophenolic Acid / Q000031:analogs & derivatives*; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013608:Tablets, Enteric-Coated
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D000077552:Basiliximab; D003404:Creatinine; D009173:Mycophenolic Acid