CHICAGO — With the goal of preventing renal complications in type 1 diabetics, nephrologists have begun to focus on subtle increases in nighttime blood pressure as a risk factor for the development of overt nephropathy.
“It is a concept we are pioneering, a very promising approach,” Dr. Daniel Batlle said at a meeting on clinical nephrology sponsored by the National Kidney Foundation.
In a prospective study, he and his associates followed 75 young type 1 diabetics without microalbuminuria at baseline for 5 years. After 2 years, none of the subjects had developed any urinary protein, but 18% of the subjects went on to develop microalbuminuria. In those who developed microalbuminuria, the mean systolic pressure during sleep increased significantly (from 109.9 to 114.9 mm Hg). This group had elevated systolic blood pressure only at night (Kidney Int. 2003;63:2319–30).
This line of research is a departure from the classic reasoning that blood pressure does not start to increase until overt proteinuria occurs in diabetics, noted Dr. Batlle, chairman of the nephrology department at Northwestern University, Chicago.
No specific treatments for mild nocturnal hypertension have been developed, but a 5-year National Institutes of Health study of 300–400 patients should shed more light on the importance of nocturnal hypertension in diabetics, said Dr. Batlle, the study's principal investigator. “Systolic [hypertension] seems to be a more powerful predictor that diastolic,” he added.
Nephrologists have long considered microalbuminuria to be the best marker for predicting progression of renal disease, but more recent studies have shown that the cumulative incidence of overt nephropathy in patients with type 1 diabetes and microalbuminuria is only about 25%. “So obviously, microalbuminuria is not as good a predictor as we thought,” he explained.
In addition to microalbuminuria, researchers also have considered histology and genetics in the search for a marker for an increased risk of nephropathy. Renal biopsies of 170 type 1 diabetics with albuminuria that regressed in some patients but progressed in others revealed that a wider glomerular basement membrane could lead to the development of proteinuria (Diabetes 2005;54:2164–71). Researchers have not yet shed light on the genetic nature of proteinuria. “We don't have a good genetic marker,” Dr. Batlle said.
A family history of nephropathy confers the greatest risk of the subsequent development of microalbuminuria. Other clinical risk factors for progression include poor diabetes control, an increase in urinary albumin excretion that is still within the normoalbuminuria range, and hyperfiltration.