Subclinical Lesions and Donor-Specific Antibodies in Kidney Transplant Recipients Receiving Tacrolimus-Based Immunosuppressive Regimen Followed by Early Conversion to Sirolimus

Transplantation 2015 [Record in progress]

Aims
To evaluate the incidence of acute and chronic histological lesions and the incidence of donor-specific antibodies (DSA) in patients receiving reduced tacrolimus (TAC) exposure with subsequent conversion to sirolimus (SRL) at 3 months after transplant.

Interventions
Patients were converted from TAC to SRL 3 months after transplant (SRL group) or maintained on TAC (TAC group).

Participants
169 kidney transplant recipients who systematically received reduced TAC exposure during the first 3 months posttransplant

Outcomes
Clinical outcomes were mean TAC concentrations, the incidence of subclinical inflammation lesions, interstitial fibrosis (IF), tubular atrophy (TA), biopsy-proven acute rejection (BPAR), proteinuria, donor-specific anti-HLA antibodies (DSA), delayed graft function (DGF) and previous BPAR.

Follow-up
24 months

CET Conclusions
This is an important paper from a distinguished centre in renal disease in which they have studied renal transplant patients entered into a multicenter randomised trial comparing conversion to sirolimus with continuing tacrolimus. This study has been confined to the low risk recipients entered into the trial from their own centre. The major trial (Silva HT et al. AJT 2013) is in the Transplant Library and basically it reported failure to show improvement in renal function with conversion to sirolimus at 24 months after transplantation. In this sub study, confined to the Pestana centre patients had biopsies at three months and then again at 24 months to look at the incidence and influence of subclinical inflammatory lesions at three months on the subsequent outcomes. 169 patients had been enrolled in the multicentre study and 140 patients were available at three months and represented the study population. The incidence of subclinical inflammatory lesions at three months was 9.3% and the incidence of interstitial fibrosis/ tubular atrophy at month 24 was 58%. This latter finding was higher in the sirolimus conversion group compared to the TAC group. There was a higher incidence of acute rejection and also proteinuria in the sirolimus converted group and a numerical, but not significant, increase in donor specific antibodies in the converted group. Other associations were black ethnicity, donor age and conversion to sirolimus in a multivariate analysis. There was no improvement in renal function at 24 months which was also a finding in the complete trial. The authors admit that this study is in low risk recipients but nevertheless these are important and carefully done observations which suggest that conversion to mTOR inhibitors may not lead to any improvement in renal function or in histological findings.

Jadad score
3

Data analysis
Modified intention-to-treat analysis

Allocation concealment
No

Quality notes
Score based on Silva HT, Felipe CR, Garcia VD, et al. “Planned randomized conversion from tacrolimus to sirolimus-based immunosuppressive regimen in de novo kidney transplant recipients.” Am J Transplant. 2013; 13(12):3155–3163.

Trial registration
None

Funding source
Industry funded