Sirolimus in renal transplant recipients with tuberous sclerosis complex: clinical effectiveness and implications for...

Tuberous sclerosis complex (TSC) is caused by constitutively activated mammalian target of rapamycin (mTOR) resulting in nonmalignant tumours of several organs and consequently renal failure. Recent reports suggest a possible beneficial role of the mTOR-inhibitor (mTOR-I) sirolimus for TSC; however, safety and efficiency of sirolimus in TSC patients after renal transplantation, both as primary immunosuppressant as well as anti-proliferative agent, are still undefined. Moreover, it is currently unknown whether the TSC mutation affects the primary immune response in these patients. In this article, we report on three TSC patients after renal transplantation who have been converted from a calcineurin-inhibitor (CNI)-based immunosuppression to sirolimus. During 2 years of follow-up, renal allograft function was stable or even improved, and no significant sirolimus-associated side-effects were noted. Beneficial effects of sirolimus against TSC were detected in the skin, along with improved spirometric measurements and an arrest of astrocytoma progression. We show that the inflammatory immune response was significantly altered in TSC patients as compared with controls and sirolimus potently affected both inflammatory cytokine production and vascular endothelial growth factor levels in these patients. Larger studies are warranted to further examine the relationship between clinical parameters and the molecular response to mTOR-inhibition in TSC patients after renal transplantation.