Sirolimus monotherapy versus sirolimus in combination with steroids and/or MMF for immunosuppression after liver transplantation

Anurag Maheshwari, Michael Torbenson, Paul J. Thuluvath

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolatemofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 ± 10 months. Preconversion renal biopsies in five of six patients showed histological features consistent with CI nephrotoxicity. Serum creatinine increased in the year prior to conversion from 1.7 ± 0.4 to 2.1 ± 0.7 mg/dl (P = 0.009) and improved thereafter (1 month, 1.7 ± 0.6, P < 0.001; 6 months, 1.6 ± 0.5, P < 0.001; last follow-up, 1.7 ± 0.9, P = 0.02); only four patients showed a significant decline in renal function after conversion. Seven (11.3%) patients experienced acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the discontinuation of sirolimus in one patient. Fifty-four adverse events occurred in 40 (67%) patients, with similar numbers of adverse events in Group A and Group B. Most episodes of rejection (5/7; 71%), adverse events (45/54; 83%), and discontinuations (5/8; 63%) occurred within 6 months of conversion. We conclude that both sirolimus monotherapy and sirolimus in combination with prednisone and/or MMF are efficacious and safe in liver transplant recipients. Conversion to sirolimus was associated with an immediate improvement in renal function that was sustained during the follow-up.

Original languageEnglish (US)
Pages (from-to)1677-1684
Number of pages8
JournalDigestive Diseases and Sciences
Volume51
Issue number10
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Fingerprint

Sirolimus
Liver Transplantation
Immunosuppression
Steroids
Kidney
Liver
Prednisone
Creatinine
Retrospective Studies
Morbidity
Biopsy
Safety
Mortality
Serum
Calcineurin Inhibitors

Keywords

  • Liver transplantation
  • Sirolimus

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Sirolimus monotherapy versus sirolimus in combination with steroids and/or MMF for immunosuppression after liver transplantation. / Maheshwari, Anurag; Torbenson, Michael; Thuluvath, Paul J.

In: Digestive Diseases and Sciences, Vol. 51, No. 10, 01.10.2006, p. 1677-1684.

Research output: Contribution to journalArticle

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abstract = "Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolatemofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 ± 10 months. Preconversion renal biopsies in five of six patients showed histological features consistent with CI nephrotoxicity. Serum creatinine increased in the year prior to conversion from 1.7 ± 0.4 to 2.1 ± 0.7 mg/dl (P = 0.009) and improved thereafter (1 month, 1.7 ± 0.6, P < 0.001; 6 months, 1.6 ± 0.5, P < 0.001; last follow-up, 1.7 ± 0.9, P = 0.02); only four patients showed a significant decline in renal function after conversion. Seven (11.3{\%}) patients experienced acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the discontinuation of sirolimus in one patient. Fifty-four adverse events occurred in 40 (67{\%}) patients, with similar numbers of adverse events in Group A and Group B. Most episodes of rejection (5/7; 71{\%}), adverse events (45/54; 83{\%}), and discontinuations (5/8; 63{\%}) occurred within 6 months of conversion. We conclude that both sirolimus monotherapy and sirolimus in combination with prednisone and/or MMF are efficacious and safe in liver transplant recipients. Conversion to sirolimus was associated with an immediate improvement in renal function that was sustained during the follow-up.",
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AB - Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolatemofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 ± 10 months. Preconversion renal biopsies in five of six patients showed histological features consistent with CI nephrotoxicity. Serum creatinine increased in the year prior to conversion from 1.7 ± 0.4 to 2.1 ± 0.7 mg/dl (P = 0.009) and improved thereafter (1 month, 1.7 ± 0.6, P < 0.001; 6 months, 1.6 ± 0.5, P < 0.001; last follow-up, 1.7 ± 0.9, P = 0.02); only four patients showed a significant decline in renal function after conversion. Seven (11.3%) patients experienced acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the discontinuation of sirolimus in one patient. Fifty-four adverse events occurred in 40 (67%) patients, with similar numbers of adverse events in Group A and Group B. Most episodes of rejection (5/7; 71%), adverse events (45/54; 83%), and discontinuations (5/8; 63%) occurred within 6 months of conversion. We conclude that both sirolimus monotherapy and sirolimus in combination with prednisone and/or MMF are efficacious and safe in liver transplant recipients. Conversion to sirolimus was associated with an immediate improvement in renal function that was sustained during the follow-up.

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