Transcriptome Changes of Chronic Tubulointerstitial Damage in Early Kidney Transplantation

Abstract

Allografts display predictable immune and fibrotic gene expression profiles, with patterns of expression gradually varying by time after transplantation. The pathology reflects differential activation of intrinsic pathways. Gene expression predated histologic damage, suggesting its possible use in early diagnostic testing.

The Molecular Phenotype of 6-Week Protocol Biopsies from Human Renal Allografts: Reflections of Prior Injury but Not Future Course

“…The inverse correlation of injury-up and injury-down changes were first described in mouse kidney isografts and shown to be augmented in allografts, and later in human kidney allograft biopsies for cause and heart transplant biopsies (23,33). Other groups have confirmed this pattern in protocol biopsies (38)(39)(40)(41)(42). This disturbance correlates with the history of DGF and with the extent of inflammation by histopathology and thus with the lesions of TCMR.…”

Transcriptional Profiling of Belatacept and Calcineurin Inhibitor Therapy in Renal Allograft Recipients

“…DEGs unique to CNI biopsies are enriched for gene sets associated with CNIT, fibrosis and CAI Only biopsies from CNI-treated patients showed significant enrichment (p < 0.05) of genes associated with CNIT (identified from the RPTE model; Table 1), published gene sets associated with chronic allograft damage and gene sets generated from unrelated renal allograft biopsies with chronic transplant injury (19). These same CAI and fibrotic gene profiles were not enriched in the biopsy samples from patients treated with belatacept.…”

Relationships among injury, fibrosis, and time in human kidney transplants

“…Studies of mRNA and miR in kidneys with fibrosis reveal that many molecular changes associated with fibrosis are related to inflammation and matrix remodeling (21)(22)(23)(24)(25). We previously reported that fibrosis in human kidney transplants was associated with transcripts expressed in certain inflammatory cells: mast cell transcripts (MCATs) such as carboxypeptidase 3 (CPA3) (26) and immunoglobulin transcripts (IGTs) representing plasma cells (27).…”