Non-Invasive Biomarker Strategy Integrating Dd-cfDNA Versus Biopsy-Based Monitoring in Kidney Transplant Recipients

The investigator hypothesizes that the combined use of 1. non-invasive biomarkers including dd-cfDNA in peripheral blood predicting anti-donor immunological activation or quiescence with 2. interactive and actionable data analytics delivered at the bedside will promote safe clinical follow-up of kidney transplant patients with less need for invasive biopsies to assess allograft rejection. It is therefore proposed a European, multicenter, prospective randomized trial comparing two strategies of follow-up: in the first, M3 biopsy decision is guided by a non-invasive, integrative dd-cfDNA-based decision support system, in the second one, a routine biopsy is performed at M3. In both groups, a biopsy is performed at M12 and whenever considered necessary by the clinician

Inclusion Criteria: 1. All men and women, age ≥18 years old. 2. Subject must be a recipient of a single renal transplant from a deceased or living donor. 3. Subject is willing and able to provide signed written informed consent and willing to comply with study procedures 4. Women of Childbearing Potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal \[defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL\]. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of clinical trial Exclusion Criteria: 1. Patients with active systemic infection that requires the continued use of antibiotics. 2. Patients with neoplasia except localized skin cancer receiving appropriate treatment. 3. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, women who are pregnant or breastfeeding or women with a positive pregnancy test on enrolment. 4. Subjects who are legally detained in an official institution. 5. Any condition that, in the opinion of the investigator, might interfere with the patient's participation in the study, poses an added risk for the patient, or confounds the assessment of the patient 6. History of multi-organ transplant (interference with rejection natural history).