Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals biological mechanisms underlying graft fibrosis and outcome after distinct immunosuppressive regimens. Homo sapiens

Intragraft transcriptional profiles were investigated in patients with tubular dysfunction to disclose subclinical mechanisms underlying graft deterioration. Moreover, we analyzed whether individualization of immunosuppression could modify this profile while improving renal function after 12 months of regimen modification. Overall design: 33 renal transplant patients were enrolled in the study considering their high urinary levels of retinol binding protein, a biomarker of proximal tubular dysfunction (PTD). They were divided in two groups regarding immunosuppressive therapy. At time zero (t0), 33 patients were biopsied and 18 patients had their immunosuppression regimen modified, namely, reduction of cyclosporine dosage and introduction of mycophenolate mofetil (MYF), while 15 patients remained under azathioprine (AZA) schema. All patients were followed-up for 12 months (t12) and then re-biopsied. Microarray experiments were performed using biopsies from 17 patients. Molecular changes due to elevated uRBP levels and immunosuppressive therapies were interpreted via transcriptional network analysis.