T. Zacher et al., Cyclosporine A sensitivity in vitro and P-glycoprotein expression in patients on dialysis and after kidney transplantation, TRANSPL IMM, 8(2), 2000, pp. 147-150
Background: In allogeneic kidney transplantation the response to cyclospori
ne A (CsA) is important for graft outcome. Although CsA therapy is controll
ed by drug monitoring to ensure therapeutic CsA levels, the sensitivity to
the effects of CsA varies among individuals. Since CsA is an antagonist of
cytostatic drugs in P-glycoprotein (Pgp)-mediated transport, increased Pgp
expression might contribute to an increased resistance to CsA. Methods: The
sensitivity of lymphocytes at three different concentrations of CsA was te
sted in a non-radioactive lymphocyte-transformation test and related to Pgp
expression as determined by flow cytometry on mononuelear cells. Five grou
ps, including healthy donors (CON; n = 25): patients on dialysis (DIAL; n =
25), patients before transplantation (PTX; n = 5) and after transplantatio
n [short-term (ATX; n = 5) and long-term (LTX: n = 25)] were investigated.
Results: In LTX, the sensitivity to CsA at 400 and 1000 ng/ml was significa
ntly different from CON and DIAL. Overall a higher sensitivity to CsA was s
een in patients after transplantation. In ATX, sensitivity to CsA was signi
ficantly higher than in PTX at a concentration of 1000 ng/ml CsA. However,
comparing all groups no significant changes in Pgp expression were noted. A
nalysing the relationship between CsA sensitivity and Pgp expression, no si
gnificant heterogeneity could be observed between the different groups. Con
clusion: In conclusion, our data suggest that in vitro testing of CsA sensi
tivity prior transplantation and Pgp expression monitoring yield independen
t results and cannot substitute for each other as predictors of graft outco
me. The differential role of each test for the evaluation of CsA sensitivit
y or resistance remains to be determined. (C) 2000 Elsevier Science B.V. Al
l rights reserved.