The use of antihypertensive agents in the management of patients with diabetic nephropathy

Based on current information, specific recommendations can be made regarding the optimal treatment of the patient with diabetic nephropathy (Table II). Treatment should be directed not only toward reducing the rate of decline in GFR, but also toward reducing the risk for cardiovascular disease complications that frequently occur in this patient population. Quality of life should also be an important goal of therapy. If possible, patients should follow a low protein, low cholesterol, diabetic diet, and tight control of blood sugars should be pursued, as long as this does not increase the frequency of severe hypoglycemic reactions. Patients with even mild hypertension should receive therapy, probably starting with an ACE inhibitor. ACE inhibition can cause hyperkalemia, particularly in patients with diabetes; however, hyperkalemia can often be controlled by adding a loop diuretic. Treatment with an ACE inhibitor may be associated with other prohibitive side-effects in some patients. In those patients, a calcium antagonist, possibly a non-dihydropyridine calcium antagonist, could be considered as alternative therapy. A calcium antagonist can also be added to an ACE inhibitor for better blood pressure control. Because of their adverse metabolic effects, thiazide diuretics should be used sparingly, if at all. In addition, retrospective, uncontrolled investigations have recently reported an association between the use of diuretics and increased mortality in patients with diabetes. Finally, a good case can be made for the use of an ACE inhibitor in normotensive patients with diabetic nephropathy. In addition to blood pressure control, modifying other vascular disease risk factors should be given a high priority. Patients should be encouraged to quit smoking, and, if possible, should be treated using an effective smoking- cessation program. In obese patients, weight reduction should be attempted with appropriate diet and exercise. Elevations in serum lipoproteins should also be aggressively treated, generally following National Cholesterol Education Program Guidelines. Clearly, for patients with early or advanced diabetic nephropathy, an integrated treatment program employing both hygienic and pharmacologic measures is most likely to be of long-term benefit.