Urine single cell RNA-sequencing in focal segmental glomerulosclerosis reveals inflammatory signatures in immune cells and podocytes

The diagnosis of focal segmental glomerulosclerosis (FSGS) requires a renal biopsy which is invasive and can be problematic in children and in some adults. We used single cell RNA-sequencing to explore disease-related cellular signatures in 17 urine samples from 12 FSGS subjects. We identified immune cells in urine predominantly monocytes and renal epithelial cells including podocytes. Analysis revealed M1 and M2 monocyte subsets and podocytes showing increased expression of genes involved in epithelial-to-mesenchymal transition (EMT). We confirmed M1 and M2 gene signatures using published monocyte/macrophage data from lupus nephritis and cancer. Using renal transcriptomic data from the Nephrotic Syndrome Study Network (NEPTUNE) we found that urine immune and EMT signature genes also showed higher expression in FSGS biopsies compared to minimal change disease biopsies. These results suggest that urine cell profiling may serve as a diagnostic and prognostic tool in nephrotic syndrome and may assist in identifying novel biomarkers and developing personalized therapeutic strategies. Overall design: single cell RNAseq of urine cells from 12 subjects with focal segmental glomerulosclerosis Contributor: The Nephrotic Syndrome Study Network (NEPTUNE) Contributor: The Accelerating Medicines Partnership in Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) consortium