Sirolimus-based triple immunosupression with antithymocyte globulin induction in expanded criteria donor kidney transplantation

Background:  Target of rapamycin inhibitors have presented similar graft and patient outcomes with no evidence of drug-induced nephrotoxicity when compared with calcineurin inhibitors. The principal aim of this study is to demonstrate the efficacy of sirolimus-based triple immunosuppression with antithymocyte globulin induction in expanded donor kidney transplantation.

Methods:  Twenty-seven primary expanded criteria donor kidney transplant recipients were recruited. The severity of kidney damage was qualified by zero-hour biopsies. Protocol biopsies were performed at 1 year to assess the chronic allograft damage. Death, graft function, proteinuria and adverse events were systematically analysed during the study period.

Results:  The mean follow up was 20.2 months. Patient and graft survival was 100% with a mean glomerular filtration rate (GFR) of 53.1 ± 4.9 mL/min at last follow up. The cumulative incidence of acute rejection was 11% at the last follow up. At 1 year, mean creatinine, GFR and proteinuria were 1.84 mg/dL, 52.3 mL/min, 651.5 mg/day, respectively. Four patients required surgical intervention due to urinary complications and recovered successfully. Two patients developed acute graft dysfunction due to acute tubular necrosis which was presumably drug related. Ten patients developed relapsing urinary tract infections and three patients had pneumonia. No infectious death occurred throughout the study period. Baseline renal structure was preserved in 13 biopsies at 1 year post transplant. Five patients demonstrated progressive but mild tubular atrophy or interstitial fibrosis in their protocol biopsies. The mean chronic allograft damage index scores at baseline and at 1 year from biopsy were 2.57 ± 0.23 and 2.83 ± 0.23, respectively (P = 0.046).

Conclusions:  Low-dose sirolimus-based triple immunosuppresion with antibody induction offered a safe clinical outcome in expanded criteria donor kidneys with the achievement of stable renal function and favourable recipient outcomes throughout the short term. However, mild progression of histological damage and increased risk of bacterial infection are a major concern. Additionally, the benefit (if any) of the low acute rejection rate on long-term graft outcome is still undetermined.