This study examined large renal tubule extracellular vesicles (LRT-EVs) isolated from urine of a 5/6 nephrectomy (5/6Nx) rat model that recapitulates many elements of human chronic kidney disease (CKD). Within weeks of 5/6Nx rats spontaneously exhibit proximal tubular damage including brush boarder shedding and the production of LRT-EVs. Analysis of the LRT-EV size and a lack of TUNEL staining in 5/6Nx rats, suggested LRT-EVs to be distinct from exosomes, microvesicles, and apoptotic bodies.