Purpose: Optimal induction and maintenance immunosuppressive
therapies in renal transplantation are still a matter of debate.Chronic
corticosteroid usage is a major cause of morbidity but steroid-free
immunosuppression (SF) can result in unacceptably high rates of
acute rejection and even graft loss.
Methods and materials: We have conducted a prospective openlabelled
clinical trial in the Geneva-Lausanne Transplant Network from
March 2005 to May 2008. 20 low immunological risk (<20% PRA, no
DSA) adult recipients of a primary kidney allograft received a 4-day
course of thymoglobulin (1.5 mg/kg/d) with methylprednisolone and
maintenance based immunosuppression of tacrolimus and entericcoated
mycophenolic acid (MPA). The control arm consisted of
16 matched recipients treated with basiliximab induction, tacrolimus,
mycophenolate mofetil and corticosteroids. Primary endpoints were
the percentage of recipients not taking steroids and the percentage
of rejection-free recipients at 12 months.Secondary end points were
allograft survival at 12 months and significant thymoglobulin and/or
other drugs side effects.
Results: In the SF group, 85% of the kidney recipients remained
steroid-free at 12 months. The 3 cases of steroids introduction were
due to one acute tubulo-interstitial rejection occurring at day 11, one
tacrolimus withdrawal due to thrombotic microangiopathy and one
MPA withdrawal because of multiple sinusitis and CMV reactivations.
No BK viremia was detected nor CMV disease. The 6 CMV negative
patients who received a positive CMV allograft had a symptomatic
primoinfection after their 6-month course valgancyclovir prophylaxis.
In the steroid-based group, 3 acute rejection episodes (acute humoral
rejection, acute tubulointerstitial Banff IA and vascular Banff IIA)
occurred in 2 recipients, 3 BK virus nephropathies were diagnosed
between 45 and 135 days post transplant No side effects were
associated with thymoglobulin infusion.In the SF group, 4 recipients
presented severe leukopenia or agranulocytosis and one recipient had
febrile hepatitis leading to transient MPA withdrawal. Discontinuation of
MPA was needed in 2 patients for recurrent sinusitis and CMV
reactivations. Patient and graft survival was 100% in both groups at
12 month follow-up.
Conclusion: Steroid-free with short-course thymoglobulin induction
therapy was a safe protocol in low-risk renal transplant recipients.
Lower rates of acute rejection and BK virus infections episodes were
seen compared to the steroid-based control group. A longer follow-up
will be needed to determine whether this SF immunosuppressive
regimen will result in higher graft and patient survival.