Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model

In contrast to blood, which has mechanisms to maintain a homeostatic internal environment, urine is more likely to reflect changes in the body. As urine accumulates all types of changes, identifying the precise cause of changes in the urine proteome is challenging and crucial in biomarker discovery. To reduce the effects of both genetic and environmental factors on the urinary proteome, this study used a rat model of adriamycin-induced nephropathy resembling human focal segmental glomerulosclerosis (FSGS) development.

Urine samples were collected at before adriamycin administration and day3, 7, 11, 15 and 23 after. Urinary proteins were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Of 23 changed proteins with disease development, 20 have human orthologs, and 13 proteins were identified as stable in normal human urine, meaning that changes in these proteins are more likely to reflect disease. Fifteen of the identified proteins have not been established to function in FSGS development. Seven proteins were selected for verification in ten more rats as markers closely associated with disease severity by western blot.

We identified proteins changed in different stages of FSGS in rat models, which may aid in biomarker development and the understanding of FSGS pathogenesis.