Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab

A 12-month randomized trial in renal transplant recipients

Diane Cibrik, Herwig Ulf Meier-kriesche, Barbara Bresnahan, You Min Wu, Goran Klintmalm, Clifton E. Kew, Paul C. Kuo, John Whelchel, David Cohen, Prabakar Baliga, Enver Akalin, Enrico Benedetti, Francis Wright, Bonnie Lieberman, Bettina Ulbricht, Stephen Jensik, Sharon Inokuchi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C2) 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 C2 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-C2 range) or group B (lower-C2 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 C2 levels are associated with improved renal function compared with higher C2 levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C2 levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalClinical Transplantation
Volume21
Issue number2
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Mycophenolic Acid
compound A 12
Cyclosporine
Kidney
Area Under Curve
Creatinine
Adrenal Cortex Hormones
Transplants
Kidney Transplantation
Multicenter Studies
Biomarkers
Steroids
Maintenance
Biopsy
basiliximab
Transplant Recipients

Keywords

  • C monitoring
  • Cyclosporine microemulsion
  • Enteric-coated mycophenolate sodium
  • High-risk recipient
  • Kidney transplant
  • Myfortic
  • Renal function

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab : A 12-month randomized trial in renal transplant recipients. / Cibrik, Diane; Meier-kriesche, Herwig Ulf; Bresnahan, Barbara; Wu, You Min; Klintmalm, Goran; Kew, Clifton E.; Kuo, Paul C.; Whelchel, John; Cohen, David; Baliga, Prabakar; Akalin, Enver; Benedetti, Enrico; Wright, Francis; Lieberman, Bonnie; Ulbricht, Bettina; Jensik, Stephen; Inokuchi, Sharon.

In: Clinical Transplantation, Vol. 21, No. 2, 03.2007, p. 192-201.

Research output: Contribution to journalArticle

Cibrik, D, Meier-kriesche, HU, Bresnahan, B, Wu, YM, Klintmalm, G, Kew, CE, Kuo, PC, Whelchel, J, Cohen, D, Baliga, P, Akalin, E, Benedetti, E, Wright, F, Lieberman, B, Ulbricht, B, Jensik, S & Inokuchi, S 2007, 'Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab: A 12-month randomized trial in renal transplant recipients', Clinical Transplantation, vol. 21, no. 2, pp. 192-201. https://doi.org/10.1111/j.1399-0012.2006.00622.x
Cibrik, Diane ; Meier-kriesche, Herwig Ulf ; Bresnahan, Barbara ; Wu, You Min ; Klintmalm, Goran ; Kew, Clifton E. ; Kuo, Paul C. ; Whelchel, John ; Cohen, David ; Baliga, Prabakar ; Akalin, Enver ; Benedetti, Enrico ; Wright, Francis ; Lieberman, Bonnie ; Ulbricht, Bettina ; Jensik, Stephen ; Inokuchi, Sharon. / Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab : A 12-month randomized trial in renal transplant recipients. In: Clinical Transplantation. 2007 ; Vol. 21, No. 2. pp. 192-201.
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abstract = "Background: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C2) 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 C2 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-C2 range) or group B (lower-C2 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 C2 levels are associated with improved renal function compared with higher C2 levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C2 levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.",
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T1 - Renal function with cyclosporine C2 monitoring, enteric-coated mycophenolate sodium and basiliximab

T2 - A 12-month randomized trial in renal transplant recipients

AU - Cibrik, Diane

AU - Meier-kriesche, Herwig Ulf

AU - Bresnahan, Barbara

AU - Wu, You Min

AU - Klintmalm, Goran

AU - Kew, Clifton E.

AU - Kuo, Paul C.

AU - Whelchel, John

AU - Cohen, David

AU - Baliga, Prabakar

AU - Akalin, Enver

AU - Benedetti, Enrico

AU - Wright, Francis

AU - Lieberman, Bonnie

AU - Ulbricht, Bettina

AU - Jensik, Stephen

AU - Inokuchi, Sharon

PY - 2007/3

Y1 - 2007/3

N2 - Background: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C2) 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 C2 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-C2 range) or group B (lower-C2 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 C2 levels are associated with improved renal function compared with higher C2 levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C2 levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

AB - Background: Cyclosporine exposure, as estimated by the area under the curve (AUC), predicts outcomes in renal transplantation. Cyclosporine concentration at two h post-dose (C2) 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 C2 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-C2 range) or group B (lower-C2 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 C2 levels are associated with improved renal function compared with higher C2 levels when used in conjunction with EC-MPS, steroids and basiliximab induction. EC-MPS with low cyclosporine C2 levels, corticosteroids and basiliximab provides excellent renal function with good efficacy even in high-risk patients.

KW - C monitoring

KW - Cyclosporine microemulsion

KW - Enteric-coated mycophenolate sodium

KW - High-risk recipient

KW - Kidney transplant

KW - Myfortic

KW - Renal function

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