Immunosuppressive Effects and Safety of a Sirolimus/Cyclosporine Combination Regimen for Renal Transplantation

Kahan, Barry D.; Podbielski, Jeanette; Napoli, Kimberly L.; Katz, Stephen M.; Meier-Kriesche, Herwig Ulf; Buren, Charles T. Van

doi:10.1016/s0022-5347(05)68892-1

Cited by 38 publications

(56 citation statements)

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“…Unlike the recent renal transplantation trial where the incidence of allograft rejection was lower in those receiving rapamycin, 14,17 in our study, no significant reduction in allograft rejection was observed in patients treated with rapamycin at later stages after transplantation. The frequency of allograft rejection may not have been high enough in our cohort to discern a significant difference between the groups.…”

Section: Discussioncontrasting

confidence: 99%

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Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy

et al. 2003

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Background-Cardiac transplantation vasculopathy is the leading cause of late death in heart transplantation recipients.Rapamycin is an immunosuppressant drug with potent antiproliferative and antimigratory effects. We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54Ϯ10 years; 4.3Ϯ2.3 years after transplantation) with severe disease. Methods and Results-At annual cardiac catheterization, patients were randomly assigned to treatment with rapamycin (nϭ22) versus continued current immunosuppression (nϭ24). Clinical characteristics including recipient age and sex, underlying cause of congestive heart failure, donor age and sex, and ischemic time were recorded. Cardiac catheterization was graded with the use of a semiquantitative scale and repeated annually. Clinically significant adverse events were defined as death, need for angioplasty or bypass surgery, myocardial infarction, and a Ͼ25% worsening of the catheterization score. These events were monitored as primary study end points. Anti-HLA class I and II antibody production and lymphocyte growth assays were measured with each biopsy. Patients selected for rapamycin had azathioprine or mycophenolate mofetil discontinued and were given rapamycin. Outcomes were compared by means of log-rank analysis. There were no significant differences in baseline characteristics. Duration of follow-up was comparable (rapamycin, 689Ϯ261; control, 630Ϯ207 days; NS). In the rapamycin group, 3 patients reached primary end points versus 14 patients in the control group (PϽ0.001). There was no difference in baseline or subsequent anti-HLA class I or II antibody production. Conclusions-In

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Section: Discussioncontrasting

confidence: 99%

“…13 Use of rapamycin in de novo kidney allograft recipients has been shown to be effective in reducing allograft rejection. 14,15 Use of rapamycin in heart transplantation recipients is more limited.…”

Section: See Pmentioning

confidence: 99%

Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy

et al. 2003

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“…There seemed to be a greater incidence of gastrointestinal side effects of diarrhea, nausea, and vomiting compared with historical controls with cyclosporine A and prednisone. 96 With sirolimus doses up to 7 mg/m 2 /d, platelet (232 v 291/nL; P ϭ .01) and WBC counts after 1 year (6.3 v 10.7/nL; P Ͻ .0001) were significantly lower than in the control group. Also, a common side effect of sirolimus treatment was myelosuppression, which was dose related and correlated strongly (r ϭ 0.89) with sirolimus trough levels.…”

Section: Clinical Trials Safetymentioning

confidence: 84%

“…In a phase II dose-escalating study of renal allograft recipients, 96 the safety profile of sirolimus in combination with cyclosporine A and prednisolone remained unchanged with up to 47 months' follow-up. No differences were found between study groups and historical controls regarding rates of viral and bacterial infections and occurrence of posttransplantation malignant diseases.…”

Section: Clinical Trials Safetymentioning

confidence: 99%

mTOR inhibitors: An overview

Neuhaus

Klupp

Langrehr

2001

Liver Transplantation

181

142

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“…This class of immunosuppressants has a novel mechanism of action that is different from all other antirejection medications that are used for transplantation (37,38). The major complications of the TOR inhibitors include hyperlipidemia, thrombocytopenia, and poor wound healing (38).…”

mentioning

confidence: 99%

Safety and Efficacy of a Calcineurin Inhibitor Avoidance Regimen in Pediatric Renal Transplantation

Harmon¹,

Meyers²,

Ingelfinger

et al. 2006

Journal of the American Society of Nephrology

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Thirty-four children were entered into a pilot trial of calcineurin inhibitor avoidance after living-donor kidney transplantation, the CN-01 study. Patients were treated with anti-CD25 mAb, prednisone, mycophenolate mofetil, and sirolimus. Twenty patients were maintained on the protocol for up to 3 yr of follow-up. One enrolled patient did not receive the transplant because of a donor problem, eight terminated because of one or more rejection episodes, four terminated because of adverse events, and one was lost to follow-up. Two grafts were lost, one as a result of chronic rejection and the other as a result of posttransplantation lymphoproliferative disorder. There were no deaths. The 6-and 12-mo acute rejection rates were 21.8 and 31.5%, respectively. GFR were stable throughout the course of the study, with a slight downward trend by 6 mo after transplantation followed by a slight upward trend to a mean of 70 ml/min thereafter. Early surveillance graft biopsies frequently showed focal interstitial mononuclear cellular infiltrates without overt vasculitis or tubulitis, but these infiltrates disappeared without treatment. Anti-HLA class I and II antibodies were detected in three patients before transplantation, and all three had acute rejections, including the two patients who lost their grafts. De novo anti-HLA Ab production occurred in only one patient after transplantation. There were two episodes of Epstein Barr virus-related posttransplantation lymphoproliferative disorder, one of which developed after the patient had been terminated from the study. It is concluded that calcineurin inhibitor-free immunosuppression can be safe and effective in pediatric living-donor renal transplantation. However, further modifications that are designed to lessen early rejection rates and decrease complications should be tested before this approach is used routinely.

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Immunosuppressive Effects and Safety of a Sirolimus/Cyclosporine Combination Regimen for Renal Transplantation

Cited by 38 publications

References 0 publications

Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy

Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy

mTOR inhibitors: An overview

Safety and Efficacy of a Calcineurin Inhibitor Avoidance Regimen in Pediatric Renal Transplantation

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