Elevated blood pressure predicts the development of persistent proteinuria in the presence of poor glycemic control, in patients with type I diabetes.

The risk of developing persistent proteinuria was studied prospectively in 376 patients, enrolled in the Diabetic Retinopathy Study, who did not have proteinuria at entry to the study. The subjects had insulin-dependent diabetes with onset before age 30, more than 5 years duration of diabetes, and a median of 3 years of follow-up for proteinuria. Persistent proteinuria developed in 55 patients, giving an overall incidence rate of 61/1000 person-years; however, the incidence rate decreased markedly after 20 years of diabetes, from 117/1000 to 23/1000 person-years. Regardless of duration, it also decreased after age 40. Among those with less than 20 years of diabetes, it decreased from 126/1000 to 28/1000 person-years; and among those with duration 20 or more years, it decreased from 44/1000 to 7/1000 person-years. High mean blood pressure quadrupled the risk of persistent proteinuria among patients with high plasma glucose levels but had little effect on the risk in patients with glucose levels below the median for the group. In conclusion, hypertension predicts the development of nephropathy particularly in those with poorly controlled diabetes. This is consistent with our hypothesis that, in individuals with predisposition to hypertension, severe hyperglycemia interacts with some mechanism underlying that predisposition and causes injury to the kidneys. The marked decrease in risk after age 40 suggests that the development of diabetic nephropathy may be limited to a window of vulnerability. While the mechanisms for these associations remain unclear, these findings have important implications for managing patients with Type I diabetes to prevent renal failure.