Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study

Abstract

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16–2.46) and a higher incidence of severe infections (1.25;1.00–1.55), but a lower risk of diabetes (0.66;0.47–0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68–1.62), reject/graft loss (0.61;0.36–1.04) and severe infections (0.76;0.56–1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.

What is the role of microbial biotechnology and genetic engineering in medicine?

“…Tacrolimus (also known as FK506) is used in clinics to prevent graft rejection and to treat skin diseases (Ordóñez‐Robles et al, 2018 ). The use of tacrolimus in the treatment of patients with liver transplants has supplanted that of cyclosporine because tacrolimus is much more potent (up to 100 times more) than cyclosporine (Bellini et al, 2024 ; Haddad et al, 2006 ). Tacrolimus is one of the most effective immunosuppressants in the treatment against the rejection of transplanted organs (Bellini et al, 2024 ; Meier‐Kriesche et al, 2006 ).…”

“…The use of tacrolimus in the treatment of patients with liver transplants has supplanted that of cyclosporine because tacrolimus is much more potent (up to 100 times more) than cyclosporine (Bellini et al, 2024 ; Haddad et al, 2006 ). Tacrolimus is one of the most effective immunosuppressants in the treatment against the rejection of transplanted organs (Bellini et al, 2024 ; Meier‐Kriesche et al, 2006 ). Unfortunately, the production yields of tacrolimus from the producing strains are very low, which significantly increases the cost of the final product (Kosec et al, 2012 ).…”