Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation.
BACKGROUND
Calcineurin inhibitors (CNIs) are the first-line immunosuppressive agents administered after liver transplantation, but they cause renal impairment. Two recent randomized trials report cellular rejection and liver graft loss when mycophenolate mofetil (MMF) monotherapy was used as a renal-sparing agent. Our experience with MMF in the same setting but with longer follow-up is described.


METHODS
In 45 patients with serum creatinine more than 120 micromol/L or creatinine clearance less than 50 mL/min, 2 g MMF per day was administered (median 29 months, 1-49 months) either as monotherapy (with all other immunosuppression withdrawn in 1 month) in 16 patients (group I) or in combination with low-dose CNI (trough tacrolimus </=5 ng/mL, cyclosporin A </=50 ng/mL) in 29 patients (18 patients without [group II] and 11 patients with [group III] previous refractory rejection [rejection after two episodes of treated rejection]).


RESULTS
In group I (median interval receiving MMF, 33 months), only one patient (6%) experienced cellular rejection, and serum creatinine normalized in five of eight patients long term. In group II (median follow-up 26.5 months), none of 18 experienced rejection, and serum creatinine normalized in 6 of 10 long term. In group III (median follow-up 34 months), 5 of 11 patients (45%) experienced further rejection, one was not steroid responsive, and serum creatinine normalized in four of eight patients long term. There was no graft loss or death as a result of rejection.


CONCLUSIONS
Our cohort with prolonged follow-up showed significant improvement in renal function with both MMF monotherapy and in combination with low-dose CNI with minimal rejection (five of six steroid responsive) and no graft loss. MMF substitution is a therapeutic strategy that deserves more extensive use in liver transplantation.
Raimondo
Maria Luisa
ML
Liver Transplant and Hepatobiliary Medicine, Royal Free Hospital, London, UK.
Dagher
Lucy
L
Papatheodoridis
George V
GV
Rolando
Nancy
N
Patch
David W
DW
Davidson
Brian R
BR
Rolles
Keith
K
Burroughs
Andrew K
AK
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000188:drug therapy*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid