Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials

Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials:
Background: Corticosteroids are increasingly used in renal transplant patients to minimize organ rejection after transplantation. In attempts to reduce corticosteroids adverse effects, transplant professionals are customary attempted to taper off, and permanently stop corticosteroids after few months of administration with other immunosuppressants.
Objective: To evaluate clinical benefits and risks of late corticosteroid withdrawal in renal transplant patients treated with tacrolimus (TAC) or mycophenolate mofetil (MMF), or both.
Methods: A meta-analysis was performed of published randomized controlled trials that reported outcomes in kidney transplant patients who were randomized to corticosteroids maintenance or late withdrawal under concomitant immunosuppression by TAC, MMF or both. Outcomes included acute graft rejection; graft failure rate; all-cause mortality; incidence of post-transplant diabetes; change in serum creatinine and total cholesterol; and change in pediatric standardized height z-score. PubMed and Google Scholar were used in literature search between 1999 and April 1, 2010. Data were combined using unweighted random effects model.
Results: Nine studies randomized 1907 patients met the inclusion criteria: TAC (n=1); MMF (n=6); both (n=2). Compared to maintenance therapy, late corticosteroid withdrawal was associated with 34% increase in the risk of acute graft rejection (95% CI for OR: 0.47–3.82); 35% and 5% reductions in the risk of graft failure and patient’s all-cause mortality (95% CI for OR: 0.26–1.60; 0.23–3.93, respectively); and 4% increase in post-transplant diabetes risk (95% CI for OR: 0.45–2.41). Late corticosteroid withdrawal was associated with substantial reduction in total cholesterol levels (mean difference: 18.1 mg/dL; 95% CI: 7.1–29.0 mg/dL), but did not reduce serum creatinine levels (‑0.00 mg/dL; 95% CI: ‑0.17 to 0.17). Stopping corticosteroids was associated with better pediatric growth outcomes.
Conclusion: Late corticosteroid withdrawal under TAC and/or MMF-lead immunosuppression after kidney transplantation could provide benefits in terms of total cholesterol, patient and graft survival, and pediatric growth. This strategy, however did not reduce the risk of acute graft rejection, post-transplant diabetes mellitus, and deterioration in serum creatinine levels.