Safety and efficacy of sirolimus in kidney transplant patients and in patients with coronary artery disease undergoing angioplasty.

Abstract

UNLABELLED:

We show the key results of our 4-year experience with sirolimus in kidney transplant patients and in nontransplanted patients undergoing coronary angioplasty.

METHODS:

Recipients of one-haplotype living-related kidney allografts were randomized to receive sirolimus (2 mg/d, n = 35) or azathioprine (2 mg/kg per day, n = 35). Recipients of fully mismatched living kidney allografts (n = 55) received sirolimus (2 mg/day). High-risk recipients of black ethnicity (n = 68) were randomized to target whole-blood trough sirolimus concentrations between 8 and 12 ng/mL or 15 to 20 ng/mL. All kidney transplant patients received cyclosporine and prednisone. Sirolimus/cyclosporine pharmacokinetic studies were performed in 40 patients receiving 2 mg (n = 20) or 5 mg (n = 20) of sirolimus 7 days after transplantation. In the coronary intervention study, 12 patients at high risk for in-stent restenosis received sirolimus for 28 days after angioplasty.

RESULTS:

The incidence of biopsy-confirmed acute rejection was 11.4% in recipients of one-haplotype living-related kidney allografts, 16.4% in recipients of fully mismatched living kidney allografts, and 15% (8 to 12 ng/mL) and 4% (15 to 20 ng/mL) in high-risk recipients of black ethnicity. Cyclosporine exposure was higher after morning administration compared to evening administration. There were poor correlations between sirolimus and cyclosporine exposures. The 4-month follow-up angiography revealed no restenosis (stenosis diameter > 50%), a late loss of 0.56 +/- 0.40 mm, and a loss index of 0.33 +/- 0.30. The follow-up 3D-intravascular ultrasound restudy showed an in-stent relative volumetric obstruction of 9.9 +/- 5.5%. Sirolimus in highly effective in preventing kidney allograft acute rejection and in-stent coronary restenosis.

• Authors: H Tedesco Silva Jr, C R Felipe, P G P Machado, R Garcia, S Motegi, B H Hosaka, N M Hanzawa, S I Park, D Casarini, V C Lima, M Franco, J O Medina-Pestana
• Journal: Transplantation proceedings (Transplant Proc) Vol. 35 Issue 3 Suppl Pg. 177S-180S (May 2003) ISSN: 0041-1345 [Print] United States
• PMID: 12742493 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Immunosuppressive Agents
• Cyclosporine
• Azathioprine
• Sirolimus

Topics

• Adult
• Angioplasty, Balloon, Coronary
• Azathioprine (therapeutic use)
• Black People
• Cadaver
• Coronary Disease (immunology, therapy)
• Cyclosporine (therapeutic use)
• Family
• Female
• Graft Rejection (epidemiology)
• Histocompatibility Testing
• Humans
• Immunosuppressive Agents (therapeutic use)
• Incidence
• Kidney Transplantation (immunology)
• Living Donors
• Male
• Risk Assessment
• Safety
• Sirolimus (therapeutic use)
• Tissue Donors
• Transplantation, Homologous (immunology)