Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Use-Long-term Follow-up of First Tuberous Sclerosis Complex Patient Treated De Novo With Sirolimus After Kidney Transplantation: A Case Report.

Mammalian target of rapamycin inhibitors (mTORI) are increasingly used in the treatment of tuberous sclerosis complex (TSC) and as immunosuppressants after organ transplantation. In TSC patients, mTORI are the treatment of choice after kidney transplantation. It is still under debate if benefits from long-term mTORI use will not be limited by side effects.

MATERIALS AND METHODS: We report long-term follow-up data of the first TSC patient after kidney transplantation treated with sirolimus de novo. In 2005, a female patient was transplanted with a kidney graft after bilateral nephrectomy due to angiomyolipoma. Initial immunosuppressive treatment consisted of antithymocyte globulin, methylprednisolone, tacrolimus, and, due to TSC diagnosis, sirolimus. Creatinine level at discharge was 1.2 mg/dL.

RESULTS: Long-term mTORI use resulted in skin lesion regression (angiofibromas, "confetti" skin lesions, shagreen patch) and disease stabilization in brain, abdominal, and chest magnetic resonance imaging/computed tomography scans. Pulmonary function tests showed improvement in restriction and slow deterioration in obstruction and diffusion parameters. Sirolimus related adverse reactions were hyperlipidemia and hypertriglyceridemia and respiratory and urinary tract infections. No gastrointestinal or hematologic symptoms occurred. Sirolimus concentrations ranged between 1.7 and 8.2 ng/mL (mean 4.01 ± 2.09 ng/mL). Since 2009 proteinuria and slow increase in creatinine level have been observed. No biopsy was performed to establish etiology and potential association with mTORI. In 2017 creatinine level was 2.2 mg/dL.

CONCLUSION: The case of the patient confirms clinical effectiveness and acceptable safety of long-term mTORI treatment. Long-term mTORI use requires meticulous patient observation to optimize dosage, achieve immunosuppressive effect, and improve TSC manifestations with minimal side effects.