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
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
Recently, early biomarkers of renal interstitial fibrosis have been identified, amongst them
 de novo expression of vimentin by tubular epithelial cells, which is an intermediate
 filament, and the translocation of beta-catenin into their cytoplasm. These markers, when
 present, suggest that the epithelial cell undergoes a phenomenon well known as "epithelial to
 mesenchymal transition" (EMT) and could behaves like a myo-fibroblast. EMT is highly
 instrumental in several models of tissue fibrosis, including in the kidney. Actually, it has
 not only been demonstrated that these markers are detectable in the renal graft at an early
 time point post-transplant (i.e. as soon as three months), but also that the intensity of
 their expression correlates with the progression of interstitial fibrosis of the graft
 between 3 and 12 months
Inclusion Criteria:

 -  Recipient of a primary or secondary deceased or living (related or not) donor kidney
 transplant and who requires basiliximab induction therapy.

 -  Cold ischemia time < 30 hours.

 -  Women of child-bearing age, even those with a history of infertility, must have had a
 negative pregnancy test during the 7 days before screening or at the time of
 screening, and must use a recognized and reliable method of contraception throughout
 the study and for 2 months after discontinuing the study treatment.

 -  Patients who want and are able to take part in the entire study, and have given their
 written consent.

 -  Patients who are registered with a French national health insurance scheme or are
 covered by such a scheme.

 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.

 Other protocol-defined inclusion/exclusion criteria may apply.