Gene expression of the renal endothelin system in renal transplant recipients on cyclosporine a based immunosuppression

Background, Immunosuppressive therapy based on cyclosporine A (CsA) is pote ntially nephrotoxic, and each dose of CsA is followed by a transient increa se in plasma endothelin (ET)-1, The aim of this study was to investigate th e effect of CsA based immunosuppressive therapy on renal gene expression of the ETA and ETB receptor subtypes and preproET-1 in human transplant needl e biopsies. Methods, Twelve living donor renal transplant recipients, median age 51.5 y ears (range 24-63 years) were included in the study. Immunosuppressive ther apy consisted of CsA, azathioprine, and prednisolone. Baseline renal cortic al needle biopsies from the living donor kidneys were obtained just before nephrectomy, Follow-up biopsies were obtained from the same transplanted ki dneys after 2-6 weeks of immunosuppressive therapy. We used a quantitative, competitive reverse transcriptase polymerase chain reaction assay to measu re renal ETA and ETB receptor subtype mRNAs as well as preproET-1 mRNA leve ls in each of the biopsies. Results, The renal ET system was not significantly altered by CsA-based imm unosuppressive therapy. Median ET, mRNA level was 185 (range 35-244) at bas eline, and 120 (11-189) amol/mu g total RNA after CsA based immunosuppressi ve therapy (P=0.11). ET, mRNA level was 506 (209-1411) at baseline, and 463 (267-1609) amol/mu g total RNA at follow-up (P=0.44) and preproET-1 mRNA l evel was 160 (112-392) before and 221 (187-361) amol/mu g total RNA after i mmunosuppressive therapy based on CsA (P=0.58). Conclusion, This study indicates that 2-6 weeks of CsA-based immunosuppress ion neither significantly influences renal gene expression of the ETA or ET B receptor subtypes nor preproET-1 in living donor renal transplant kidneys .