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

Abstract

Immunosuppressive therapy based on cyclosporine A (CsA) is potentially nephrotoxic, and each dose of CsA is followed by a transient increase in plasma endothelin (ET)-1. The aim of this study was to investigate the effect of CsA based immunosuppressive therapy on renal gene expression of the ET(A) and ET(B) receptor subtypes and preproET-1 in human transplant needle biopsies. Twelve living donor renal transplant recipients, median age 51.5 years (range 24-63 years) were included in the study. Immunosuppressive therapy consisted of CsA, azathioprine, and prednisolone. Baseline renal cortical needle biopsies from the living donor kidneys were obtained just before nephrectomy. Follow-up biopsies were obtained from the same transplanted kidneys after 2-6 weeks of immunosuppressive therapy. We used a quantitative, competitive reverse transcriptase polymerase chain reaction assay to measure renal ET(A) and ET(B) receptor subtype mRNAs as well as preproET-1 mRNA levels in each of the biopsies. The renal ET system was not significantly altered by CsA-based immunosuppressive therapy. Median ET(A) mRNA level was 185 (range 35-244) at baseline, and 120 (11-189) amol/microg total RNA after CsA based immunosuppressive therapy (P=0.11). ET(B) mRNA level was 506 (209-1411) at baseline, and 463 (267-1609) amol/microg total RNA at follow-up (P=0.44) and preproET-1 mRNA level was 160 (112-392) before and 221 (187-361) amol/microg total RNA after immunosuppressive therapy based on CsA (P=0.58). This study indicates that 2-6 weeks of CsA-based immunosuppression neither significantly influences renal gene expression of the ET(A) or ET(B) receptor subtypes nor preproET-1 in living donor renal transplant kidneys.