Abstract
We recently developed a model of accelerated kidney disease through genetic modification of the Dahl salt‐sensitive (S) rat. The novel congenic model [S.SHR(11)] demonstrates significantly more renal injury including glomerulosclerosis, tubulointerstitial damage and increased renal vascular hypertrophy, culminating in a more rapid decline in kidney function compared to the already highly susceptible S rat. The model is currently being used for the identification of novel biomarkers associated with onset and progression of hypertension related kidney disease. Through the use of Multidimensional Protein Identification Technology, or MudPIT, a proteomic analysis of urine exosomes obtained under low (moderate hypertension) and/or high‐salt (severe hypertension) conditions yielded several candidate protein biomarkers (e.g. MAPK1, ODF2, APOB) which are currently being validated via western blot analyses. Validated biomarkers identified in the rat will be tested on urine exosomes obtained from a unique human chronic kidney disease (CKD) population currently being collected at the University of Mississippi Medical Center. In summary, genetic modification of the S rat generated a model of accelerated kidney disease that may provide a unique experimental model to identify novel biomarkers of onset and progression of hypertension related kidney disease in humans. Supported by NIH/NHLBI HL094446 (MRG).
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