Dear Ayman,

Please read the following text:

Tacrolimus vs. cyclosporine

A meta-analysis of RCTs reported reduced acute rejection and better graft survival with tacrolimus compared to CsA (22). For every 100 patients treated for the first year with tacrolimus rather than CsA, 12 would be prevented from having acute rejection, two would be prevented from having graft failure, but five would develop NODAT. The RCTs in the meta-analysis combined studies of patients receiving the original CsA preparation and cyclosporine A microemulsion (CsA-ME). This study also showed that lower tacrolimus were associated with higher relative risk of graft loss, while higher levels of tacrolimus were associated with an increased risk for NODAT.

Randomized controlled trials comparing tacrolimus with CsA-ME using concomitant azathioprine and corticosteroids, but no induction, have shown reduced acute rejection with tacrolimus; for example, 22% vs. 42% at 12 months, respectively (p < 0.001) (23). The difference in acute rejection between the two CNIs could no longer be observed with concomitant induction and MMF instead of azathioprine; for example 4% vs. 6%, for tacrolimus vs. CsA-ME, respectively (24) or 7% vs. 10% at 6 months, respectively (25) when C2 monitoring of CsA was also employed. Furthermore, there is evidence that subclinical rejection (acute rejection changes in protocol biopsy not indicated by a change in kidney function) is more effectively prevented by tacrolimus and MMF compared to CsA and MMF; 15% vs. 39% (p < 0.05) (26).

A very large multicenter RCT in de novo KTRs (n = 1645; the Symphony study) showed superior graft function, better prevention of acute rejection (12.3%) and superior graft survival (96.4%) at 12 months with daclizumab induction and low-dose tacrolimus (C0 3–7 ng/mL). The comparator groups included low-dose CsA and low-dose sirolimus, both with daclizumab induction and standard-dose CsA without induction. All patients received MMF (2 g/day) and corticosteroids (27).

There is no uniform definition of NODAT used in the literature. Therefore, the reported incidences of NODAT vary to a great extent. Studies reporting a difference between tacrolimus and CsA in the incidence of NODAT, impaired glucose tolerance, or the use of antidiabetic treatment, favor CsA; for example 17% vs. 9% (p < 0.01; tacrolimus vs. CsA) (25). Others have found lower incidences and no significant difference (24,28). One reason for the variation in findings may be differences in the use of corticosteroids as maintenance medication and treatment of acute rejection. Indeed, use of a steroid-free regimen has been associated with a lower incidence of NODAT (29).

Overall, there is moderate-quality evidence for a net benefit of tacrolimus vs. CsA (see Evidence Profile and accompanying evidence in Supporting Tables 8–10). There is no clear evidence of differences in terms of patient mortality, incidence of malignancy, infection, delayed onset of graft function or blood pressure. There is evidence that cholesterol, low-density lipoprotein cholesterol (LDL-C) (but not high-density lipoprotein cholesterol [HDL-C]), acute rejection and graft loss are higher with CsA vs. tacrolimus. However, there is also evidence that NODAT is more common with tacrolimus than CsA, so that there is clear trade-off in the different patient-relevant outcomes with these two CNIs.

This text was taken from a publication entitled "Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients "  published in 

American Journal of Transplantation Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients ,Volume 9, Issue Supplement s3, pages S1–S155,November 2009.

To view the full publication, please use the following link:

http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2009.02834.x/full

Hoping this will be helpful,

Rafik