Paper Title
Renal Function and Regulatory T-cell Number Assessment in Kidney Transplanted Patients Receiving Cyclosporine A Versus Sirolimus After 2 Years

Abstract
Background: Mammalian target of rapamycin (mTOR) inhibitors provide both lower nephrotoxic and better tolerogenic properties compared to calcineurin inhibitor (CNI) in the era of kidney transplants. Objectives: We aimed to evaluate the conversion effects of cyclosporine A (CsA) with sirolimus (SRL) from the point of both nephrotoxicity and tolerogenocity via calculation of GFR and T-regulatory (Treg) cell numbers, respectively 2 years after kidney transplantation. Patients and Methods: 88 primary kidney recipients who were under transcription of clinically adjusted doses of MMF plus steroids, adaptively randomized to remain on CsA (n=59) or switch to SRL (n=29) about 3-6 months post-transplant. Before conversion and at year 2 after transplantation GFR was calculated and 2 subsets of Tregs including CD4+CD25+FoxP3+ and CD8+CD28- cells were counted by 3-color flow cytometry. Results: GFR decreased in CsA group 2 years after transplantation (P=0.002). The frequency of CD4+CD25+FoxP3+ (P<0.001, P=0.018) and CD8+CD28- (P=0.028, P<0.001) Tregs were significantly increased in CsA and SRL groups, respectively 2 years after transplantation. In both drug groups, the changes of CD8+CD28- Tregs remained significant after controlling the likely confounding effects of GFR changes, acute rejection episodes, urinary tract infection, respiratory infection, CMV and BK infection (P=0.006). Conclusions: The maintenance use of CNIs may be replaced by mTOR inhibitors to yield better renal function without any decrease in Treg numbers that prevent both acute and chronic rejection and play some pivotal roles in tolerance induction. Keywords - Kidney Transplantation, Regulatory T cells, Cyclosporine A, Sirolimus, GFR