The impact of cyclosporine dose reduction with or without the addition of rapamycin on functional, molecular, and histological markers of chronic allograft nephropathy
| Autor: | G R Bicknell, Saunders Rn, M. L. Nicholson |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty Pathology Kidney Glomerulus Urology Renal function Gene Expression Nephropathy Transforming Growth Factor beta1 chemistry.chemical_compound Chronic allograft nephropathy Transforming Growth Factor beta medicine Humans Transplantation Homologous Prospective Studies Coloring Agents Sirius Red Sirolimus Kidney Tissue Inhibitor of Metalloproteinase-2 Transplantation Tissue Inhibitor of Metalloproteinase-1 Staining and Labeling business.industry Middle Aged medicine.disease Ciclosporin Kidney Transplantation medicine.anatomical_structure chemistry Chronic Disease Cyclosporine Matrix Metalloproteinase 2 Drug Therapy Combination Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Transplantation. 75:772-780 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-200303270-00008 |
| Popis: | BACKGROUND Overexposure to cyclosporine is a risk factor for chronic allograft nephropathy (CAN) and dose reduction has been advocated. The purpose of this study was to determine the impact of adding the non-nephrotoxic immunosuppressant, rapamycin, after cyclosporine dose reduction in renal-allograft recipients with CAN. METHODS Thirty-one patients with biopsy-confirmed CAN were prospectively randomized to receive a 40% cyclosporine dose reduction with (rapamycin, n=16) or without (control, n=15) the addition of rapamycin 2 mg/day. Renal function and side-effect parameters were assessed. Patients had renal allograft biopsies taken at recruitment and after 6 months. Glomeruli were isolated from these and underwent total mRNA extraction followed by RT-PCR-ELISA to assess transforming growth factor-beta1, collagen III, TIMP-1, TIMP-2, and matrix metalloproteinase-2 expression. Samples were also stained with Sirius red and the percentage interstitial volume fraction quantified by computerized histomorphometric analysis. Data are presented as mean (+/-SD). RESULTS Patient characteristics and cyclosporine trough levels after dose reduction (rapamycin 68 [+/-21] vs. control 56 [+/-19] ng/mL, P=NS) were similar in both groups. Rapamycin patients had a significant fall in Cr-51 radioisotope glomerular filtration rate (31.6 [+/-8.9] to 27.3 [+/-8.6] mL/min, P |
| Databáze: | OpenAIRE |
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