Different effect of cyclosporine and tacrolimus on renal expression of P-glycoprotein in human kidney transplantation.
OBJECTIVE
To investigate the differential effects of cyclosporine (CsA) and tacrolimus (TAC) on renal expression of P-glycoprotein (P-gp) in a cohort of kidney transplant recipients.


METHODS
We enrolled 78 cadaveric kidney transplant recipients recurring basal immunosuppressive protocol with prednisone + mycophenolate mofetil + calcineurin inhibitor (CsA or TAC).


RESULTS
We performed a 3-year analysis of 60 patients. There was no difference in age, gender, or cold ischemic time between two groups, Serum creatinine, urine protein, and blood fat levels of the CsA group were significantly higher than the TAC group (P < .05), while the creatinine clearance was remarkably lower than the TAC group (P < .05). The incidence of tubular atrophy, arteriohyalinosis, and interstitial fibrosis and nephrotoxic lesions among the CsA group were higher than the TAC group, as well as the chronic allograft nephropathy (CAN) Banff score (P < .05). P-gp was predominantly present in the a tubular apical membrane, basal membrane, and cytoplasm. The intensity and extent of tubular staining score in the CsA group were lower compared with the TAC group (P < .01 and P < .05, respectively).


CONCLUSIONS
Less P-gp expression in the CsA group than the TAC group may be the molecular action pathway of the high incidence of CsA nephrotoxicity and CsA-induced CAN. This study perhaps unraveled a novel interpretation that the differences of CsA and TAC on long-term allograft survival were due to increases dynamic effects of CsA at the exposures employed in this study.
Yu
X
X
First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zhang
B
B
Xing
C
C
Sun
B
B
Liu
M
M
Zhang
W
W
Gu
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D016559:Tacrolimus