Key result
Renal transplant recipients on cyclosporin A demonstrated significant downregulation of ETA receptor mRNA compared to normal controls (median 0.024 vs 0.2 amol/microgram; P=0.003).
Why the study?
Does cyclosporin A therapy alter endothelin receptor mRNA levels in renal transplant recipients compared to controls?
Observational (n=19)
Does cyclosporin A therapy alter endothelin receptor mRNA levels in renal transplant recipients compared to controls?
Absolute Event Rate: 0.024% vs 0.2%
p-value: p=0.003
Cyclosporin A therapy in renal transplant recipients is associated with significant downregulation of ETA receptor mRNA, suggesting a potential mechanism for its renal vasoconstrictor effects.
May link cyclosporin A to renal vasoconstriction via ETA downregulation; hypothesis-generating and should not change practice.
Despite intensive investigation, a pathophysiological role for the endogenous vasoconstrictor peptide endothelin (ET) remains elusive. The kidney is particularly sensitive to the effects of ET, which are mimicked by the administration of cyclosporin A (CsA), and animal models suggest a role for ET in the vasoconstrictive effects of CsA. Using a recently validated novel fluorescent quantitative RT-PCR assay to enable the direct study of human renal biopsies, we have quantified mRNA for the two known ET receptor subtypes ETA and ETB in cortical tissue from three groups of patients: renal transplant recipients on CsA (n = 7), those with native renal disease (n = 5) and normal controls (n = 7). Median and mRNA levels (amol/microgram total RNA) were 0.024, 0.17 and 0.2 respectively for ETA and 0.57, 0.64 and 0.96 for ETB. These values indicate significant downregulation of ETA (P = 0.003) but not ETB (P = 0.104) mRNA in the transplant group. These results provide the first demonstration of a perturbation in the human ET system at tissue level in a pathophysiological situation, and suggest that the deleterious renal vasoconstrictor effects of CsA might be ameliorated by selective ETA receptor antagonism in the future. This study also illustrates the feasibility of ex vivo analysis of human diagnostic material at the molecular level.
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Karet et al. (1996) conducted an observational in Renal transplant recipients on cyclosporin A (n=19). Cyclosporin A (CsA) vs. Native renal disease and normal controls was evaluated on ETA receptor mRNA levels (amol/microgram total RNA) (p=0.003). Renal transplant recipients on cyclosporin A demonstrated significant downregulation of ETA receptor mRNA compared to normal controls (median 0.024 vs 0.2 amol/microgram; P=0.003).
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