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Twenty-three insulin-dependent diabetics with proteinuria (3.3 g/day: range 0.3 to 8.9) and azotemia (creatinine clearance: 58 mL/min, range 30 to 112) were tested for 24-h mean arterial blood pressure; instantaneous heart rate variations to a computerized protocol involving timed ventilation, assumption of upright posture, and Valsalva maneuver; plasma fibrinogen, viscosity, fibrinolytic activity, and plasminogen activator inhibitor. These were to test the hypothesis that autonomic dysfunction is associated with altered concentrations of plasma fibrinogen, fibrinolytic activity, viscosity, and plasminogen activator inhibitor. We have previously shown the absence of a correlation between level of blood pressure, clinical and standard laboratory testing, and the results of the autonomic function testing protocol used in this study. In this group of patients, plasma fibrinogen concentration was correlated (positively) with mean arterial pressure and (negatively) with heart rate variation in response to the Valsalva maneuver. The greater the mean arterial pressure or the worse the Valsalva results, the higher the plasma fibrinogen concentration. In addition, patients with one or no abnormal autonomic function tests had a mean fibrinogen of less than 400 mg/dL compared to the group of patients with two or more abnormal tests who had a mean fibrinogen of 500 mg/dL. In patients with demonstrated parasympathetic abnormalities, postural heart rate variation testing also discerned a differential in plasma fibrinogen. Lower concentration of plasminogen activator inhibitor throughout the day, and greater fibrinolytic activity in the morning were also noted to be present in patients with abnormal heart rate response to the Valsalva maneuver. We conclude that there are relationships between high blood pressure, autonomic function, and hemostatic factors favoring thrombogenesis that may be related by common mechanisms and treatments in the diabetic with kidney disease.

Relationship Between Autonomic Function and Plasma Fibrinogen, Viscosity, and Elements of Fibrinolytic Activity in Diabetic Nephropathy