Do cyclosporin profiles provide useful information in the management of renal transplant recipients?
BACKGROUND
This study investigated the relationships between cyclosporin A (CsA) blood levels and episodes of renal allograft rejection and nephrotoxicity following renal transplantation, with the aim of establishing whether CsA profiles provided more useful information than single CsA blood levels in respect of these relationships.


METHODS
One hundred and sixty-two profiles were performed over 16 months in 40 patients and analysed retrospectively. Blood samples were taken at 0, 2, 4, 6 and 8 h after the morning CsA dose. Rejection episodes were diagnosed by renal biopsy and CsA nephrotoxicity by a fall in serum creatinine 1 week after a cut in CsA dose.


RESULTS
The mean area under the curve (AUC) was lower for profiles performed at the time of rejection (3821 h.ng/ml) than that of a matched group of non-rejecting profiles (5479 h.ng/ml; P < 0.02). An AUC above 6400 h.ng/ml significantly discriminated rejection from non-rejection, whereas pre-dose and peak CsA concentrations did not have such discriminating cut-off values. A comparison of CsA-toxic and non-toxic profiles showed that there were no significant differences between mean CsA concentrations nor between the mean AUCs of these groups.


CONCLUSIONS
We conclude that basing CsA dosing on CsA profiles could help to avoid some early episodes of rejection without increasing the risk of nephrotoxicity.
Bowles
M J
MJ
Renal Transplantation Unit, Hammersmith Hospital, London, UK.
Waters
J B
JB
Lechler
R I
RI
Williams
G
G
D000328:Adult; D016572:Cyclosporine / Q000097:blood* / Q000506:poisoning / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000506:poisoning / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine