INTRODUCTION: Despite high early graft-survival rates after kidney transplantation (KT), long-term graft survival is still limited in time under immunosuppression based on steroids, calcineurin inhibitors (CNI) and antiproliferative agents. Therefore, conversion to mTOR inhibitors (mTORi) has been proposed to reduce CNI-associated nephrotoxicity and to decrease cardiovascular risk on KT recipients. Changes in immunosuppression treatment may also have an impact on lymphocyte subpopulations
METHODS: We designed a prospective study to evaluate the long-term immunological impact of tacrolimus to mTORi conversion in 29 KT recipients compared with 16 KT recipients maintained on tacrolimus per clinical practice. We evaluated renal function, HLA antibodies and peripheral blood lymphocyte subsets at inclusion and 3, 12 and 24 months later. The immunophenotype of 20 healthy subjects was also analyzed for reference.
RESULTS: At follow up, renal function remained stable in both groups and proteinuria increased slightly in the mTORi group (308 g/g vs. 156 g/g in tacrolimus group, p=0.007). Two patients in the mTORi group developed de novo HLA donor-specific antibodies (DSA) and none in the control group (7 vs 0%, p=0.53). Overall both groups of patients showed a progressive increase in T regulatory cells, but the restricted analysis of patients recruited within the first 18 months post-KT showed increase in regulatory T cells only in those converted to mTORi (p<0.001). Patients treated with mTORi showed a decrease of total B cells and naïve B cells, except for those converted to mTORi without steroids. mTORi patients showed a significant decrease in transitional B cells (p<0.001) compared to those on tacrolimus, even patients who did not receive steroids. Natural Killer NKG2A+ cells increased in mTORi patients compared to tacrolimus (p<0.001), reaching healthy subjects´ percentages.
CONCLUSIONS: In summary, patients who switched to an mTORi displayed a significant redistribution of peripheral blood lymphocyte subpopulations that might influence graft outcomes. The co-administration of steroids modified some of these changes.
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