Transplant Trial Watch

Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus.

Gallon L, Traitanon O, Sustento-Reodica N, et al.

Kidney International. 2015 Apr; 87(4): 828-38


Aims
To investigate the immunologic effects of conversion from tacrolimus to sirolimus in renal transplant recipients.

Interventions
All patients were administered with alemtuzumab, methylprednisolone and a steroid free regimen of tacrolimus (TAC) and mycophenolate mofetil (MMF). Patients were then randomised to either continue with the TAC/MMF treatment or convert to a sirolimus and MMF regimen.

Participants
30 adult kidney transplant recipients.

Outcomes
Outcomes included estimated glomerular filtration rate, allograft rejection, T-cell subtype analysis, donor specific alloreactivity and a gene expression analysis.

Follow-up
12 months

CET Conclusions
This is an interesting small study where renal transplant patients who were part of a randomised trial comparing tacrolimus with sirolimus conversion after 12 months were examined for their T cell profiles and in particular the percentage of T reg cells as defined by CD4+ 25+Foxp3+. Patients were selected at 12 months for study with peripheral blood being collected at regular intervals and T cell alloactivity was also measured with the IFN-γ ELISPOT. Sirolimus conversion did lead to an increase in T reg cells in comparison with patients maintained on tacrolimus, who showed a decrease in indirect alloreactivity which was increased in the patients who were converted to sirolimus. No histological differences were found in the biopsies taken at 24 months post randomisation. Molecular profiles of the biopsies at 24 months again suggested some changes in the proinflammatory response. Thus differences were demonstrated in the sirolimus converted patients compared to tacrolimus maintained patients but no impact on renal function was observed in 30 months of follow up. We will see many of these types of observations but this is a carefully done study and as the evidence mounts more information will be available which may allow a practical application.

Quality notes
Quality assessment not appropriate.

Trial registration
NCT00866879

Funding source
Non-industry funded