289ACEIs and ARBs
ACEIs and ARBs are RAS blockers, with both cardioprotective and renoprotective
effects. They reduce cardiac and vascular remodeling and myocardial fibrosis, as
well as intraglomerular pressure and proteinuria [ 4 , 5 ]. Therefore, they are not only
very effective antihypertensive agents, but they are also beneficial in patients with
heart failure, post-myocardial infarction, and proteinuric CKD [ 5 ], in whom they
can prevent cardiovascular mortality and CKD progression, respectively.
Adverse effects of ACEIs and ARBs include hypotension, acute kidney injury,
and hyperkalemia. Caution is required when using these drugs in patients with bilat-
eral renal artery stenosis, volume depletion, and concurrent use of NSAIDs or other
RAS inhibitors. Monitoring of serum creatinine and potassium is indicated after
starting treatment, especially in such high-risk cases [ 5 ]. The use of these drugs in
women of child-bearing age should be balanced with the risk of pregnancy, since
they are potentially teratogenic [ 24 ].
Most available ACEIs have active moieties that are largely excreted in the urine.
Fosinopril and trandolapril are partially (approximately 50%) excreted by the liver,
such that the blood levels are less influenced by kidney failure than levels of other
ACEIs which are predominantly excreted by the kidneys. Since ACEIs are generally
titrated to achieve optimal clinical effect, the mode of excretion is not regarded as a
major factor in dosing. If hyperkalemia occurs in CKD patients taking a renal-
excreted ACEI, possible interventions include dietary advice, reducing the dose, or
adding a potassium-losing diuretic [ 24 ]. If strategies to minimize hyperkalemia
(Table 18.2) fail to maintain serum potassium concentrations below 5.6 mEq/L, the
RAS inhibitor should be discontinued, and another class of antihypertensive drugs
should be used instead [ 25 ].
Virtually all guidelines recommend ACEIs/ARBs as first-line therapeutic agents
in hypertensive CKD patients, regardless of proteinuria levels and diabetic status [ 5 ,
6 , 18 – 21 , 24 ]. However, some guidelines suggest that these drugs are particularly
preferable in CKD patients with micro- or macroalbuminuria [ 24 , 26 ], in which they
Table 18.2 Strategies to minimize risk of hyperkalemia caused by RAS inhibitors in patients with
CKD [ 25 ]
Wherever possible, discontinue drugs that can impair renal potassium excretion (e.g., NSAIDs,
including selective COX-2 inhibitors)
Prescribe a low-potassium diet; advise patients to avoid use of salt substitutes that contain
potassium
Prescribe thiazide diuretics (and/or loop diuretics if estimated GFR is <30 mL/min/1.73 m^2 )
Prescribe sodium bicarbonate to correct metabolic acidosis; decrease dose of ACEI or ARB
Measure serum potassium level 1 week after initiating ACEI or ARB therapy or after increasing
the dose
If patient is taking some combination of an ACEI, an ARB, and a MR antagonist, discontinue
one and recheck serum potassium level
Do not exceed a 25-mg daily dose of spironolactone when used in combination with an ACEI
or an ARB18 Treatment of Hypertension in Light of the New Guidelines: Pharmacologic...