Patient-Specific Considerations
There are many factors that influence the clinical management of the diabetic patient with renal insufficiency. Several common patient considerations that the pharmacy practitioner should evaluate are described in this section.
Hypertension: Hypertension is frequently seen in diabetic patients, especially in those with decreased renal function. In addition, the progression of renal dysfunction is closely related to the elevation in blood pressure. Consequently, it is important that the effects of antihypertensive medications be considered before selecting the most appropriate agent.
Christlieb proposed a step approach to antihypertensive therapy in diabetics with or without concurrent diabetic complications. Recommended step 1 agents include angiotensin-converting enzyme inhibitors (ACE) or calcium channel blockers. The angiotensin-converting enzyme inhibitors are preferred antihypertensive agents in diabetic patients for several reasons. Recent studies have shown that the ACE inhibitors in combination with captopril and enalapril decrease the amount of microalbuminuria in both hypertensive and normotensive diabetics with microalbuminuria or persistent proteinuria. These results suggest that angiotensin-converting enzyme inhibition may be beneficial, even at the earliest stage of diabetic nephropathy. In addition, Ravid et al. concluded that ACE inhibition offers long-term protection against the development of nephropathy in NIDDM patients who have microalbuminuria, and it stabilizes renal function in previously untreated patients with impaired renal function. Other beneficial qualities of the angiotensin-converting enzyme inhibitors include no adverse effects on glucose metabolism or lipid levels and a reduction in the occurrence of impotence.
Calcium channel blockers are also efficacious for the hypertensive diabetic patient and have no inherent adverse metabolic effects. If hypoaldosteronism is present or if the patient is hyporeninemic, a calcium channel blocker may be preferred as step 1 therapy. If an ACE inhibitor or a calcium channel blocker does not sufficiently decrease the blood pressure, a diuretic can be added as step 2 therapy. If edema is present, a diuretic should be included in step 1 therapy. Thiazide diuretics are effective until the patient’s creatinine clearance declines to 40 – 50 mL/min, at which time a loop diuretic may be more effective.
In addition to beneficial effects, adverse effects of antihypertensive medications must also be considered when evaluating the diabetic patient’s drug therapy. Adverse effects of angiotensin-converting enzyme inhibitors in patients with renal failure include hyperkalemia and further compromise of renal function. Hypertensive patients with renal disease, specifically severe renal artery stenosis, have developed increases in serum creatinine and BUN after reduction of blood pressure with ACE inhibitors. Therefore, renal function and potassium levels should be monitored during the first few weeks of ACE-inhibitor therapy. Impaired renal function can also decrease elimination of certain ACE inhibitors. Dosage reduction may be necessary for quinapril, benazepril, ramipril and lisinopril in patients with declining renal function.
Diuretics have been shown to adversely affect electrolyte, cholesterol and glucose levels. Thus, serum electrolyte, glucose and lipid levels should be monitored frequently in diabetic patients with renal dysfunction. In patients with renal dysfunction, potassium-sparing diuretics can cause severe hyperkalemia and should be avoided. Beta-blockers may adversely affect glucose and lipid metabolism. Blockade of beta receptors can cause diminished symptoms of hypoglycemia — primarily palpitations, anxiety and tremors — as well as delays in recovery from hypoglycemia. However, cardioselective beta-blockers (e.g., metoprolol, atenolol) may have fewer adverse effects than do noncardioselective beta-blockers (e.g., propranolol) for most hypertensive patients.
Increases in triglyceride levels and decreases in high-density lipoprotein cholesterol levels are also associated with beta-blockade. However, beta-blockers with intrinsic sympathomimetic activity or alpha-blocking activity do not adversely affect lipids. In addition, beta-blockade may also aggravate peripheral vascular disease, which is a diabetic complication.