Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival

Herwig Ulf Meier-Kriesche, Bettina J. Steffen, Alice H. Chu, Jacqueline J. Loveland, Robert D. Gordon, Jonathan A. Morris, Bruce Kaplan

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

To evaluate the association between a regimen of cyclosporine microemulsion (CsA) + sirolimus (Rapa) treatment versus CsA and mycophenolate mofetil (MMF) and renal allograft survival, we analyzed 23 016 primary recipients reported to the Scientific Registry of Transplant Recipients between January 1, 1998 and July 26, 2003. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models correcting for demographic and clinical covariates were used to estimate the relative risks for CsA+Rapa versus CsA+MMF-treated patients reaching study endpoints. Subgroup analyses were conducted for recipient ethnicity and donor type. CsA+Rapa was associated with significantly lower graft survival (74.6% vs. 79.3% at 4 years, p = 0.002) and death-censored graft survival (83.7% vs. 87.2%, p = 0.003) compared to CsA+MMF. In multivariate analyses, CsA+Rapa was associated with a significantly increased risk for graft loss, death-censored graft loss and decline in renal function (HR = 1.22, p = 0.002; HR = 1.22, p = 0.018 and HR = 1.25, p <0.001, respectively). Similar results were obtained in recipient ethnicity and donor type subgroups. In summary, CsA+Rapa was associated with significantly worse graft survival and death-censored graft survival compared to CsA+MMF, and likely reflects full-dose CsA+Rapa. Outcomes regarding alternative strategies of Rapa utilization with reduced CsA, with alternative agents or with no calcineurin inhibitor cannot be extrapolated from these data.

Original languageEnglish (US)
Pages (from-to)2058-2066
Number of pages9
JournalAmerican Journal of Transplantation
Volume4
Issue number12
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Mycophenolic Acid
Graft Survival
Sirolimus
Cyclosporine
Allografts
Kidney
Tissue Donors
Transplants
Kaplan-Meier Estimate
Proportional Hazards Models
Registries
Multivariate Analysis
Demography

Keywords

  • Acute rejection
  • Graft survival
  • Mycophenolate mofetil
  • Renal function
  • Renal transplantation
  • Sirolimus

ASJC Scopus subject areas

  • Immunology

Cite this

Meier-Kriesche, H. U., Steffen, B. J., Chu, A. H., Loveland, J. J., Gordon, R. D., Morris, J. A., & Kaplan, B. (2004). Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival. American Journal of Transplantation, 4(12), 2058-2066. https://doi.org/10.1111/j.1600-6143.2004.00624.x

Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival. / Meier-Kriesche, Herwig Ulf; Steffen, Bettina J.; Chu, Alice H.; Loveland, Jacqueline J.; Gordon, Robert D.; Morris, Jonathan A.; Kaplan, Bruce.

In: American Journal of Transplantation, Vol. 4, No. 12, 12.2004, p. 2058-2066.

Research output: Contribution to journalArticle

Meier-Kriesche, HU, Steffen, BJ, Chu, AH, Loveland, JJ, Gordon, RD, Morris, JA & Kaplan, B 2004, 'Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival', American Journal of Transplantation, vol. 4, no. 12, pp. 2058-2066. https://doi.org/10.1111/j.1600-6143.2004.00624.x
Meier-Kriesche, Herwig Ulf ; Steffen, Bettina J. ; Chu, Alice H. ; Loveland, Jacqueline J. ; Gordon, Robert D. ; Morris, Jonathan A. ; Kaplan, Bruce. / Sirolimus with neoral versus mycophenolate mofetil with neoral is associated with decreased renal allograft survival. In: American Journal of Transplantation. 2004 ; Vol. 4, No. 12. pp. 2058-2066.
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abstract = "To evaluate the association between a regimen of cyclosporine microemulsion (CsA) + sirolimus (Rapa) treatment versus CsA and mycophenolate mofetil (MMF) and renal allograft survival, we analyzed 23 016 primary recipients reported to the Scientific Registry of Transplant Recipients between January 1, 1998 and July 26, 2003. Univariate Kaplan-Meier analysis and multivariate Cox proportional hazard models correcting for demographic and clinical covariates were used to estimate the relative risks for CsA+Rapa versus CsA+MMF-treated patients reaching study endpoints. Subgroup analyses were conducted for recipient ethnicity and donor type. CsA+Rapa was associated with significantly lower graft survival (74.6{\%} vs. 79.3{\%} at 4 years, p = 0.002) and death-censored graft survival (83.7{\%} vs. 87.2{\%}, p = 0.003) compared to CsA+MMF. In multivariate analyses, CsA+Rapa was associated with a significantly increased risk for graft loss, death-censored graft loss and decline in renal function (HR = 1.22, p = 0.002; HR = 1.22, p = 0.018 and HR = 1.25, p <0.001, respectively). Similar results were obtained in recipient ethnicity and donor type subgroups. In summary, CsA+Rapa was associated with significantly worse graft survival and death-censored graft survival compared to CsA+MMF, and likely reflects full-dose CsA+Rapa. Outcomes regarding alternative strategies of Rapa utilization with reduced CsA, with alternative agents or with no calcineurin inhibitor cannot be extrapolated from these data.",
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AU - Meier-Kriesche, Herwig Ulf

AU - Steffen, Bettina J.

AU - Chu, Alice H.

AU - Loveland, Jacqueline J.

AU - Gordon, Robert D.

AU - Morris, Jonathan A.

AU - Kaplan, Bruce

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