Safety and efficacy of sirolimus in kidney transplant patients and in patients with coronary artery disease undergoing angioplasty.
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.
Nephrology Division, Hospital do Rim e Hipertensão, UNIFESP, São Paulo, Brazil. helio@nefro.epm.br
H
H
Tedesco Silva
C R
CR
Felipe
P G P
PG
Machado
R
R
Garcia
S
S
Motegi
B H
BH
Hosaka
N M
NM
Hanzawa
S I
SI
Park
D
D
Casarini
V C
VC
Lima
M
M
Franco
J O
JO
Medina-Pestana
D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D001379:Azathioprine / Q000627:therapeutic use; D044383:Black People; D002102:Cadaver; D003327:Coronary Disease / Q000276:immunology / Q000628:therapy*; D016572:Cyclosporine / Q000627:therapeutic use; D005190:Family; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D018570:Risk Assessment; D012449:Safety; D020123:Sirolimus / Q000627:therapeutic use*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D020123:Sirolimus