Endothelial Factors and Diabetic Nephropathy

Abstract

The rising incidence and prevalence of chronic kidney disease (CKD) (glomerular filtration rate <60 mL/min per 1.73 m2) is a major public health concern (U.S. Renal Data System 2010, http://www.usrds.org). Hypertension is the second leading cause of end-stage renal disease (ESRD) in the U.S. and is also a major contributor to diabetic renal disease, which is the leading cause of CKD and ESRD (U.S. Renal Data System 2010). The diabetes-related ESRD annual incidence rate has been decreasing since 1996, suggesting that the net increase in diabetes-related ESRD may be secondary to the documented pandemic of type 2 diabetes (1,2). In the general population, CKD predicts death and cardiovascular disease (CVD) events, independently of traditional cardiovascular risk factors such as age, sex, prior CVD, diabetes, hypertension, dyslipidemia, and proteinuria (3). CKD in patients with type 2 diabetes is independently associated with an ∼8–10% annual absolute risk for death and CVD (4). The majority of patients with CKD will die of a CVD event before they reach end-stage renal failure and dialysis treatment (5), and an estimated glomerular filtration rate <60 mL/min is now classified as a major independent risk factor for CVD. Endothelial dysfunction has been implicated as a potential major mechanism for renal chronic microvascular complications both in diabetic and nondiabetic patients with albuminuria. There is a general assumption of a final common biological pathway that results in diabetic kidney disease and renal failure. As shown in Fig. 1, hyperglycemia and hypertension interact at the glomerulus, resulting in glomerular hypertension and, as a consequence, proteinuria, glomerular and interstitial tissue fibrosis (6), progressive decline in glomerular filtration rate, and finally renal failure. Figure 1 Principal mechanisms of diabetic glomerulopathy. Hyperglycemia and hypertension interact at the glomerulus, resulting in glomerular hypertension, progressive glomerular and interstitial tissue fibrosis, and decline …