Single-Cell Profiling of Tubular Epithelial Cells in Adaptive State in the Urine Sediment of Patients With Early and Advanced Diabetic Kidney Disease.

Introduction: Tubular epithelial cells (TECs) under adaptive state (aTECs) have been frequently reported in the injured kidney closely associated with disease progression. However, whether aTECs is present in the urine of patients with diabetic kidney disease (DKD) and its clinical implication have not been assessed. Methods: Urine samples from patients with early and advanced DKD were collected and subjected to single-cell RNA sequencing (scRNA-seq). Kidney single nucleus RNA-seq, spatial scRNA-seq, and bulk RNA-seq datasets were employed to reconstruct their local environment and to delineate differences between shed cells and local residence. Results: Most urinary TEC in patients with DKD are under adaptive states. Whereas the composition of urinary TEC is consistent in early and advanced DKD, a higher ratio of aTECs under progenitor and fibrosis state is defined in early DKD. Trajectory inference reveals that some aTECs are early derivatives of injured proximal tubule (PT). Spatial mapping reveals that proliferative and fibrosis aTECs reside close to the glomerulus region. Systemic evaluation of different states of urinary aTECs in patients of diverse-cause kidney injury suggests that the ratio of progenitor or proliferative aTECs to fibrosis aTECs is of diagnostic value. Conclusion: Urine is an underestimated source of aTECs providing us noninvasive manner to interrogate the injured state of tubule. The ratio of fibrosis aTECs and progenitor or proliferative aTECs in urine features tubular injury state and may help improve DKD diagnosis.