Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial.
BACKGROUND
Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN.


METHODS
Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months.


RESULTS
SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55 micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89 micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36): 84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001).


CONCLUSIONS
Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival.
Meier
Markus
M
Transplantation Center, University of Luebeck, School of Medicine, Germany. markus.meier@innerel.uni-luebeck.de
Nitschke
Martin
M
Weidtmann
Britta
B
Jabs
Wolfram J
WJ
Wong
Waichi
W
Suefke
Sven
S
Steinhoff
Juergen
J
Fricke
Lutz
L
D000328:Adult; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000009:adverse effects
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus