Urinary Exosomal miRNAs as Non-Invasive Biomarkers Linked to Podocyte Morphometry in CKD

Chronic kidney disease (CKD) is a major global health burden leading to a loss of kidney function via podocyte damage, a non-regenerative renal cell type. Early detection of podocyte injury is crucial but remains limited, highlighting the need for non-invasive biomarkers. Therefore, we analysed urinary exosomal microRNAs (miRNAs) in relation to podocyte morphology in biopsies from 65 CKD patients, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and healthy controls. Global profiling distinguished CKD patients from controls, with miR-606 consistently upregulated and miR-431 downregulated. In podocytopathies, MCD displayed a predominantly suppressed miRNA profile, with miR-141, miR-429, and miR-660 as key candidates, whereas FSGS exhibited elevated miR-181c, miR-3610, miR-663b, miR-4651, and miR-429. Super-resolution morphometry revealed diffuse foot process effacement in MCD and heterogeneous, focally disrupted architecture in FSGS, providing a structural context for the molecular findings. Regression analyses linked these miRNAs to filtration slit density and length, proteinuria, and 25-Hydroxy-vitamin-D3 levels, integrating molecular, structural, and clinical readouts. These results define a coherent miRNA signature of podocyte injury that distinguishes CKD entities and correlates molecular changes with disease severity. Combining urinary exosomal miRNAs with morphometric analysis facilitates early, non-invasive identification of podocyte damage, enabling earlier therapeutic intervention in podocytopathies.