Acute rejection episodes (ARE) have been one of the major causes of graft loss and morbidity in renal transplantation and with the judicious combination of efficacious immunosuppressive drugs, the incidence and severity of ARE have currently been significantly reduced.
Aim: This study investigates the impact of quadruple immunosuppression including induction with Antithymocyte Globulin (ATG) or interleukin 2 receptor antibody (IL2Rab), followed by maintenance therapy with steroids, mycophenolate mofetil (MMF) and a calcineurin inhibitor (CNI), on ARE in renal transplant recipients.
Methods: 175 renal transplants done over 2 years with a follow up period of 6 to 18 months were analyzed regarding immunosuppressive regimens, donor type, HLA mismatches and delayed graft function, to correlate with the incidence, severity and response to therapy of ARE. 82 patients (HLA mismatches >4) received ATG, 87 patients (HLA mismatches 1-3) received IL2Rab (Basiliximab) and 6 patients (No HLA mismatches) received no drug as induction therapy. Maintenance immunosuppression included triple drug therapy with steroid, MMF and CNI of which alternate patients received cyclosporine (n=80) or tacrolimus (n=71) while 24 patients received other combinations including azathioprine or rapamicin. There were 99 male and 76 female recipients of age groups, <18years (n=24), >60 years (n=26) and 18 to 60 years (n=125). 122 patients received kidneys from live donors while 53 received from deceased donors of which 15 had delayed graft function (DGF).
Results: The acute rejection rate was 26/175 (14.8%) of which 17 (65.3%) occurred within the first 3 months and 12 (46.1%) were severe steroid resistant rejections needing OKT3 or plasma exchange therapy. 15 (18.2%) patients in the ATG group developed ARE compared to 11 (12.6%) in the IL2 group and there was no significant difference in ARE among the different maintenance protocols. Subjects with 4 or more HLA mismatches displayed more ARE (25%) compared with those with 3 or less (6.9%). Deceased donor recipients had a higher ARE (18.8%) compared with live donor recipients (13.1%) and subjects with DGF had a higher incidence of ARE (33.3%) than those without them (13.1%). Subjects below the age of 18 years had higher incidence of ARE (29.1%) compared to those between 18 and 60 years (15.2%) and those above the age of 60 years had no ARE. Quadruple immunosuppression including induction with ATG or IL2Rab, followed by triple drug maintenance therapy, reduced ARE to below 15%. Higher HLA mismatches, deceased donor, DGF and recipient age below 18 were observed to be major risk factors for the development of ARE.