Nephron-deficient HSRA rats exhibit renal injury with age but have limited renal damage from streptozotocin-induced hyperglycemia.

Hypertension and diabetes are the greatest factors influencing the progression of chronic kidney disease (CKD). Investigation into the role of nephron number in CKD alone or with hypertension has revealed a strong inverse relationship between the two; however, not much is known about the connection between nephron number and diabetic kidney disease. The heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and hypertension and diabetes on CKD.

Whole genome sequencing and novel candidate genes for CAKUT and altered nephrogenesis in the HSRA rat.

The HSRA rat is a model of congenital abnormalities of the kidney and urogenital tract (CAKUT). Our laboratory has used this model to investigate the role of nephron number (functional unit of the kidney) in susceptibility to develop kidney disease as 50-75% offspring are born with a single kidney (HSRA-S), while 25-50% are born with two kidneys (HSRA-C). HSRA-S rats develop increased kidney injury and hypertension with age compared with nephrectomized two-kidney animals (HSRA-UNX), suggesting that even slight differences in nephron number can be an important driver in decline in kidney function.