Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce angiotensin action. Angiotensin, a powerful hormone, has many actions, the most important of which is constriction of small blood vessels, leading to a rise in blood pressure and therefore in the pressure of blood within the glomerular capillaries in the kidneys. Lowering this pressure may well be the mechanism by which these drugs tend to slow progression of kidney failure.
The effects of ACEIs differ from those of ARBs in several important respects. It is even conceivable that taking drugs from both classes is more effective than taking just one or the other alone. Unfortunately, side-to-side comparisons of these two classes of drugs have not been performed, because the drug industry has no interest in such trials. These drugs are also effective in reducing urinary protein excretion in the nephrotic syndrome, and they also slow progression of chronic renal failure even when added to a low-protein diet.
Many clinical trials have demonstrated slowed progression with ACEIs, and more recently with ARBs, particularly in patients who have large amounts of urinary protein. Yet surprisingly, some recent evidence has indicated that ACEIs are no more effective than calcium channel blockers (see Chapter 9) in slowing the progression of diabetic kidney disease. Whether ACEIs and ARBs have unusual "renoprotective" effects remains unsettled. The bulk of evidence indicates that they do. However, with prolonged administration, urinary protein loss resumes in nearly half the patients, and they subsequently develop worsening kidney function.
An increasing number of patients, particularly older men, exhibit a sharp deterioration of kidney function when placed on ACEIs or ARBs. The majority of patients with severe renal failure exhibit a smaller drop in glomerular filtration rate (GFR; usually manifested as a rise in creati-nine concentration) when they are placed on these drugs. This drop presages subsequent slower progression. In other words, the more that GFR falls initially, the less it will fall subsequently. Patients who are dehydrated, as a result of diuretic treatment or gastrointestinal fluid loss, and patients who have heart failure and are taking these drugs, are particularly susceptible to a drop in GFR and may have a severe decrease in renal function.
Cough is a common side effect of ACEIs (though not of ARBs). Frequently, the cause is not identified, and doctors may prescribe extensive testing for pulmonary or laryngeal disease. Once the drug is withdrawn, the cough subsides in a few weeks.
Chapter 12 considers the problem of high blood potassium with these classes of drugs.
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