Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients

Exclusion Criteria

• •Recipient of multi-organ transplantation, including dual kidneys, or who have previously received non renal transplant organ.
• •Patients receiving a graft from a non-heart-beating donor.
• •Anti-HLA antibody levels ≥ 20% in the last 3 months before the inclusion.
• •ABO incompatible graft or with positive cross match T.
• •Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy.
• •Known hypersensitivity or contraindications to mycophenolic acid, cyclosporine or lactose.
• •Known hypersensitivity or contraindications to macrolides or drugs of the mTOR inhibitor class.
• •HIV seropositive, or active chronic hepatitis B (HBs Ab) or C. Results obtained during the 6 months before the inclusion are accepted. Recipients from donors with hepatitis B or C will be excluded.
• •Patients with thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin \< 8g/dL at the inclusion visit.
• •ASAT, ALAT or total bilirubin ≥ 3 UNL.
• •Uncontrolled severe infection, severe allergy requiring an acute or chronic treatment.
• •Patients with a malignant disease or previous malignancy in the past 5 years, with the exception of excised basal cell or squamous cell carcinoma and in situ cervical cancer treated.
• •Medical or surgical condition, with the exception of the transplantation, which in the investigator's opinion could exclude the patient.
• •Women who are pregnant, breastfeeding or of reproductive age and refuse or are unable to use a recognized and reliable method of contraception.
• •Patients with symptoms of significant mental or somatic disease. Inability to cooperate or communicate with the investigator.
• •Patients under supervision or guardianship or any patient subject to legal protection
• •Randomization criteria:
• •Eligibility criteria (no later than 4 months post-transplantation:
• •Renal graft biopsy performed at M3 and adequate histological material sent within the deadline for the determination of EMT.
• •Woman of child-bearing potential, even in case of a history of infertility, must use a recognized and reliable method of contraception throughout the study and for 2 months after discontinuing the study treatment.
• •Non-eligibility criteria (no later than 4 months post-transplantation):
• •Acute rejection histologically proven between transplantation and randomization (local reading).
• •Acute subclinical rejection diagnosed on the M3 biopsy (except borderline lesions) (local reading).
• •Positive anti-donor antibodies at M3.
• •Estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73 m2 (MDRDa).
• •Proteinuria ≥ 1 g/24h.
• •Severe hyperlipidemia: total cholesterol ≥ 9.1 mmol/L (≥ 350 mg/dL) and/or triglycerides ≥ 8.5 mmol/L (≥ 750 mg/dL) despite appropriate lipid-lowering therapy.
• •Thrombocytopenia (≤ 75000/mm3), absolute neutrophil count (≤ 1500/mm3), leukocytopenia (≤ 2500/mm3) and/or hemoglobin \< 8 g/dL.
• •ASAT, ALAT or total bilirubin ≥ 3 UNL.
• •Medical or surgical condition which in the investigator's opinion might exclude the patient.