GENE EXPRESSION OF THE RENAL ENDOTHELIN SYSTEM IN RENAL TRANSPLANT RECIPIENTS ON CYCLOSPORINE A BASED IMMUNOSUPPRESSION

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Abstract

Background.

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 ETA and ETB receptor subtypes and preproET-1 in human transplant needle biopsies.

Methods.

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 ETA and ETB receptor subtype mRNAs as well as preproET-1 mRNA levels in each of the biopsies.

Results.

The renal ET system was not significantly altered by CsA-based immunosuppressive therapy. Median ETA mRNA level was 185 (range 35-244) at baseline, and 120 (11-189) amol/μg total RNA after CsA based immunosuppressive therapy (P=0.11). ETB mRNA level was 506 (209-1411) at baseline, and 463 (267-1609) amol/μg total RNA at follow-up (P=0.44) and preproET-1 mRNA level was 160 (112-392) before and 221 (187-361) amol/μg total RNA after immunosuppressive therapy based on CsA (P=0.58).

Conclusion.

This study indicates that 2-6 weeks of CsA-based immunosuppression neither significantly influences renal gene expression of the ETA or ETB receptor subtypes nor preproET-1 in living donor renal transplant kidneys.

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