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Diabetes Care, Vol 15, Issue 9 1205-1215, Copyright © 1992 by American Diabetes Association
Diabetic nephropathy. Metabolic versus hemodynamic considerations
TH Hostetter
Department of Medicine, University of Minnesota, Minneapolis 55455.
Not all patients with diabetes develop clinically significant nephropathy
and, for this reason, attention has begun to focus on the risk factors for
development of this serious complication. These risk factors have not been
quantified to the same degree as those factors associated with more common
progressive vascular diseases, such as atherosclerosis. However, studies of
pathogenesis and clinical and epidemiological surveys of diabetic
nephropathy point to numerous risk categories. Glycemic control, genetic
and familial predispositions, renal and glomerular enlargement, glomerular
hyperfiltration, and capillary and systemic hypertension can be invoked as
contributors to this disease process. This review focuses on hemodynamic
alterations and their role in the development and progression of diabetic
nephropathy. Increases in GFR, largely driven by increases in plasma flow
and capillary pressure, appear in early IDDM and NIDDM. This abnormality of
renal vascular control probably is derived from alterations in several
vasoactive control systems. In addition, the elevations in capillary
pressure may be damaging to the glomerular capillaries. Arterial
hypertension is not necessarily present before clinical nephropathy
appears; however, it is a usual concomitant of progressive diabetic renal
disease. The strongest evidences for the roles of altered systemic and
renal hemodynamics in the progression of diabetic renal disease are
clinical and experimental studies demonstrating attenuation of the disease
process by lowering systemic and capillary pressures with antihypertensive
agents, and dietary and glycemic modifications. Thus, although multiple
factors probably interact to determine risk for the development of diabetic
nephropathy, hemodynamic forces are a particularly important contributor
and are especially amenable to therapeutic intervention.

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Copyright © 1992 by the American Diabetes Association.
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