Relationship between calcineurin inhibition and plasma endothelin concentrations in cyclosporine-A-treated kidney transplant patients.
OBJECTIVE
The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects.


METHODS
In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake.


RESULTS
Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P<0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P<0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P<0.01), although CsA doses and concentrations were not different between these two groups.


CONCLUSIONS
We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.
Büchler
M
M
Department of Nephrology and Clinical Immunology, Tours University Hospital, Tours, France.
Leibenguth
P
P
Le Guellec
C
C
Carayon
A
A
Watier
H
H
Odoul
F
F
Autret-Leca
E
E
Lebranchu
Y
Y
Paintaud
G
G
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D019703:Calcineurin / Q000097:blood; D065095:Calcineurin Inhibitors; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D016232:Endothelins / Q000097:blood*; D005260:Female; D005886:Gingival Hypertrophy / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D065095:Calcineurin Inhibitors; D016232:Endothelins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin