Chapter 23 Transplant - immunosuppression & rejection

23.1 Immunosuppression

Contemporary immunosuppressive regimes (basiliximab, pred, MMF, low-dose tacro) are supported by the ELITE-Symphony trial:

ELITE-Symphony (2007): - comparing standard-dose CsA vs. low-dose tacro vs. low-dose CsA vs. low-dose sirolimus.

Alternative regimes designed to avoid or minimise steroids and CNIs have been tested:

BENEFIT (2016): - CsA vs. belatacept (high- and low-dose groups). At 7 years, graft suvival, patient survival and GFR were higher in the belatacept groups.

HARMONY (2016): - rATG with steroid withdrawal vs. basiliximab with steroid withdrawal vs. basliximab with maintenence steroid in patients with low immunological risk. rATG was non-inferior (for acute rejection); fewer cases of diabetes in steroid-withdrawal groups.

3C (2014): - alemtuzumab (steroid-free, low-CNI, low-MMF) vs. basiliximab induction then re-randomisation at 6 months to tacro vs. sirolimus. Less rejection in the alemtuzumab group with similar rates of infection in the first 12 months. The comparison between tacro and sirolimus reported separately showed no difference in eGFR at 18 months but more infections and rejection with sirolimus.

CONVERT (2009): - sirolimus vs. CNI in maintenance phase. In patients with GFR > 40 ml/min, in the sirolimus group: GFR at 2 yrs was higher, risk of malignancy was lower, proteinuria was higher. Recruitment of patients with GFR < 40 halted early due to excess adverse events in sirolimus group.

Non-adherance is not infrequent and predicts renal outcomes.

Nevins et al. (2014): - electronic monitoring of adherence to immunosuppressive medications after kidney transplant. Early non-adherance was associated with acute rejection and graft loss.

23.2 Desensitisation

Two landmark trials showed that desensitisation offers a survival advantage to patients (comparted to matched cohort waiting for a compatible kidney):

Montgomery et al. (2011): - single-centre outcomes after desensisation in HLAi transplants.

Orandi et al. (2016): - multi-centre outcomes after desensitations in HLAi transplants.

23.3 Rejection

Nickeleit et al. (1998): - case-series of ~100 patients with acute cellular rejection. “Vascular rejection” (with endarteritis) was less responsive to steroid treatment but responded equally well to treatment with TDAs - compared to rejection without endarteritis.