A Transcriptional Blueprint for Human and Murine Diabetic Kidney Disease
- Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California
- Corresponding author: Vivek Bhalla, .
Among the end-organ complications that ravage patients afflicted with diabetes, kidney disease is associated with the highest morbidity and mortality (1,2). Diabetic kidney disease is the most common cause of chronic kidney disease (CKD) and end-stage renal disease in the U.S. and the world (3). While tighter glycemic control and the use of inhibitors of the renin-angiotensin-aldosterone system (in types 1 and 2 diabetes) have helped to slow the progression of diabetic kidney disease, the beneficial effects are modest (4). Moreover, an increase in the prevalence of type 2 diabetes (4) and the high cardiovascular risk associated with CKD and end-stage renal disease (5–7) suggest that diabetic kidney disease will absorb a disproportionate fraction of scarce health care resources in the coming decades.
Basic research to understand the pathogenesis of this disease and to develop novel therapies has been slowed by the lack of reliable mouse models that fully recapitulate the severity of the human condition. In recent years, the Animal Models of Diabetic Complications Consortium sponsored by the National Institutes of Health put forth two position papers outlining the pros and cons of various rodent models of diabetic kidney disease based on histological and clinical criteria (8,9). However, in terms of gene expression, it is unknown to what degree these data are applicable to humans. Perhaps particular strains of diabetic mice may accurately reflect specific elements of …