Cellcept

Fifty-one consecutive adult patients (≥ 18 years) who received a kidney transplant were included between March 2019 and August 2019 at the Erasmus MC, Rotterdam, the Netherlands. Written informed consent was obtained from all patients and all living donors before inclusion. All patients could be included, except for patients who also received different organ transplants (i.e. combined transplants). The study was performed in accordance with the declaration of Helsinki (2013) and was approved by the institutional review board of the Erasmus MC (Medical Ethical Review Board number 2018-035).
Donor kidneys in the study included both deceased donor organs and living donor organs (living related donors and living unrelated donors). Kidneys obtained from deceased donors were subjected to either Hypothermic Machine Perfusion (HMP), Normothermic Machine Perfusion (NMP) or Static Cold Storage (SCS).
All patients received induction therapy with either basiliximab (Simulect; Novartis Pharma, Basel, Switzerland), or rATG (Thymoglobulin, Sanofi-Genzyme), or alemtuzumab (Campath, Sanofi-Genzyme, Cambridge, MA). The maintenance immunosuppressive therapy consisted of mycophenolate mofetil (Cellcept; Roche Pharmaceuticals, Basel, Switzerland), glucocorticoids and tacrolimus (Prograft; Astellas Pharma, Leiden, the Netherlands).

The following immunosuppressive drugs were used to suppress the immune system of the animals: Mycophenolate mofetil (MMF) powder for infusion (20mg/kg) (CellCept, Roche, Woerden, The Netherlands), tacrolimus concentrate for infusion (5 mg/ml) (Prograft, Astellas Pharma BV, Leiderdorp, The Netherlands) and oral solution of prednisolone sodium phosphate (5 mg/ml) (Hospital Pharmacy, UMCN St Radboud, Nijmegen, The Netherlands). This regimen is similar to the immunosuppressive treatment of patients undergoing solid organ transplantation. To prevent opportunistic infections, all animals received an antibiotic prophylaxis of amoxicillin supplemented with oral suspension of clavulanic acid (250 mg and 62.5 mg per 5 mL, respectively) (Pharmachemie BV, Haarlem, The Netherlands). Oseltamivir phosphate (OSP; 10mg/Kg) was added to the regimes of ferrets receiving antiviral therapy and was provided by Hoffman-La Roche LtD. (Tamiflu, Basel, Switzerland). Preparation of the drugs was done as previous described [5 (link)].

Mycophenolate mofetil (MMF; CellCept®, Roche Pharmaceuticals, Basel, Switzerland) was administered at a dose of 20 mg/kg daily from 1 day prior to 6 days post-transplant (Figure 7A) (21 (link)). MMF was resuspended in 5% glucose solution at a concentration of 20 mg/ml. Animals were weighed prior to injection and an appropriate volume of MMF was administered intra-peritoneally using an insulin syringe. Vehicle-treated animals were administered the corresponding volume of 5% glucose solution only.

Data of patients followed in the Division of Rheumatology of Children's Hospital of Fudan University between December 2015 and December 2017 were included in this study. Patients were enrolled if they fulfilled the following criteria: concentration data for AUC estimation available, diagnosis of SLE according to the American College of Rheumatology classification criteria (Tan et al., 1982 (link); Hochberg, 1997 (link)); treatment with MMF at an initial dosage of 20–40 mg/kg/d twice daily, with a maximum of 1.5 g/d, in addition to prednisolone and hydroxychloroquine (HCQ); treatment with MMF (mycophenolate mofetil capsules (Cellcept^®, Roche Pharmaceuticals, Inc, Palo Alto) or mycophenolate mofetil dispersible tablets (Saikeping, Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.)) at a stable dose for at least 10 weeks. Patients were excluded if they were treated with drugs known to effect clinical response, such as cyclosporine, tacrolimus, or methotrexate. Patients' data such as demographics and SLE disease activities were collected at the time of PK evaluation. Only a single time data from each patient were included. The study protocol was approved by the Fudan Children's ethics committee.