Urinary cell transcriptomics and acute rejection in human kidney allografts

Area of Science:

• Nephrology
• Genomics
• Molecular Biology

Background:

• RNA sequencing (RNA-Seq) is crucial for analyzing gene expression, understanding disease mechanisms, and identifying biomarkers.
• Kidney allograft rejection involves complex transcriptional changes in both biopsies and potentially accessible urinary cells.

Purpose of the Study:

• To investigate gene expression and biological pathways in kidney allograft biopsies and urinary cells during acute rejection.
• To determine if urinary cell gene expression patterns reflect biopsy transcriptional profiles in T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR).

Main Methods:

• RNA-Seq was performed on 57 urine samples and 49 kidney allograft biopsies from recipients with TCMR, AMR, or No Rejection.
• Differential gene expression, pathway analysis, and gene set enrichment analysis were conducted across diagnoses and biospecimens.

Main Results:

• Unique and shared gene signatures associated with TCMR and AMR were identified compared to No Rejection.
• Gene Set Enrichment Analysis showed enrichment of biopsy signatures in corresponding urine samples, regardless of patient origin.
• Urinary cells exhibited a more diverse cellular landscape, with a notable enrichment of immune cell types compared to biopsies.

Conclusions:

• RNA-Seq of urinary cells and biopsies identifies enriched gene signatures and pathways linked to TCMR and AMR.
• Genomic differences between TCMR and AMR, and between biopsies and urinary cells, were revealed.
• Urinary cell RNA-Seq offers a non-invasive approach to complement biopsy analysis in kidney allograft rejection assessment.