Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized, controlled study.
BACKGROUND
Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept).


METHODS
A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal.


RESULTS
In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (-0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4 micromol/L, P=0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L, P=0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P=0.03), with no graft loss.


CONCLUSIONS
Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.
Abramowicz
Daniel
D
Hôpital Erasme, Bruxelles, Belgium.
Manas
Derek
D
Lao
Mieczyslaw
M
Vanrenterghem
Yves
Y
Del Castillo
Domingo
D
Wijngaard
Peter
P
Fung
Samson
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002784:Cholesterol; D009173:Mycophenolic Acid