Nitric Oxide (NO) Activity and Diabetic Nephropathy
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
Experimental data suggest that oxidative stress and endothelial dysfunction are key players
in the pathogenesis of diabetic nephropathy. In the last few years the investigators were
able to establish a method to assess endothelial function of the renal vasculature in humans
and started to systematically study a variety of cardiovascular disorders known to be
associated with endothelial dysfunction in other vascular beds, including hypertension,
hypercholesterolemia and type-2 diabetes. In patients with type-2 diabetes the investigators
could demonstrate that despite unaltered basal and stimulated NO-activity, the renal response
to the antioxidant vitamin C was more pronounced compared to control subjects. These data
suggest that oxidative stress is increased in the renal vasculature of diabetic patients.
Furthermore, NO-activity in diabetic patients appears to be upregulated to compensate for the
increase in oxidative stress. This hypothesis is supported by the demonstration of increased
endothelial nitric oxide synthase (eNOS) expression in kidney biopsies of diabetic patients.
The major focus of the investigators' current research activities is to assess the role of
endothelial dysfunction in the very early stages of diabetic nephropathy. To this end,
patients with increased fasting glucose or metabolic syndrome will be studied in comparison
with an age-matched control group. Endothelial function and the role of oxidative stress will
be assessed in the renal vasculature in all groups. In parallel, the investigators will study
endothelial function in the forearm by venous occlusion plethysmography and in the retinal
vasculature by scanning laser doppler flowmetry to dissect regional differences in the
regulation of endothelial function. Further aspects include the role of microalbuminuria,
glomerular hyperfiltration, and endogenous inhibitors of NO synthase such as
NG,NG-Dimethyl-L-Arginine (ADMA). In a therapeutic approach, the investigators will determine
the effects of various antioxidant treatment strategies on endothelial function and their
potential role in the prevention of diabetic nephropathy.