Immunological risk stratification and tailored minimisation of immunosuppression in renal transplant recipients

Abstract

Background: The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear.

Methods: This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression.

Results: Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk).

Conclusions: Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Keywords: Basiliximab; Corticosteroid-withdrawal; Mycophenolate mofetil; Renal transplantation; Tacrolimus.

Fig. 1

Tacrolimus trough levels (ng/mL) obtained over study period. Levels measured by liquid chromatography-tandem mass spectrometry for each immunological risk group are given (line at median, upper and lower quartiles, range, cross indicates mean)

Fig. 2

Patient and graft survival (Kaplan-Meier estimates) and function. a Patient survival with a functioning graft. b Graft survival by immune risk group. c Graft survival by donor type in low-risk and d high-risk patients. Numbers at risk at various time points is given below each graph. Graph beyond 400 days should be interpreted with caution due to low ‘numbers at risk’

Fig. 3

Graft function between low and high risk groups as assessed by calculated CKD-Epi eGFR at 3, 6, 12, 24 and 36 month time points. Comparisons at each time point non-significant by one-way ANOVA with Bonferroni multiple comparisons test (P 0.92, 3 m; P 0.99, 6 m; P 0.99, 12 m; P 0.99, 24 m; P 0.99, 36 m) and repeated measures ANOVA with mixed effects model analysis

Fig. 4

Biopsy-proven acute rejection (BPAR) rates. Kaplan-Meier estimates for BPAR by immune risk group (a), donor type in low-risk (b), and in high-risk (c) recipients. Numbers at risk at various time points is given below each graph. Graph beyond 400 days should be interpreted with caution due to low ‘numbers at risk’