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antihypertensive combinations apparently in a patient with RH keeping the follow-
ing points in mind.
A few points deserve special focus in the pharmacologic management of RH
patients with CKD:
- Salt restriction and volume regulation are central parts of the management of RH
in patients with CKD. As a part of the definition of RH, diuretics are sine qua
non of therapeutic armamentarium in hypertension. While thiazide and thiazide-
type diuretics constitute the mainstay of diuretic therapy used in hypertension,
patients with CKD differs in this regard. Efficacy of thiazides diminishes once
the creatinine clearance value falls below 50 ml/min [ 28 ]. Thus, loop diuretics
are the diuretic of choice in patients with stages 3–5 CKD (when GFR <30 ml/
min). GPs should be aware of this shift of diuretic choice in patients with CKD
and should be able to change thiazide to furosemide or other loop diuretics
timely in patients with deteriorating kidney function. Continuous monitoring of
weight changes and edema formation in advanced stages of CKD may help
adjusting the dose of the loop diuretics.
Contrary to the classical belief, some evidence, albeit limited, has shown that
thiazide diuretics may be as effective as furosemide in stages 4–5 CKD [ 29 ].
Combination of the latter two may even be a more effective way to lower blood
pressure, particularly in hypervolemic patients [ 30 ]. - Some antihypertensive medications require dose adjustment according to creati-
nine clearance. Failure to do so may lead to appearance of adverse effects and
nonadherence. Most ACE inhibitors are renally excreted and consequently
require dosage adjustment in case of diminished GFR with exceptions of dually
excreted ACE inhibitors, fosinopril and trandolapril. When aiming maximally
tolerated doses of ACE inhibitors, this condition should be kept in mind by the
GP. In contrast to ACE inhibitors, angiotensin receptor blockers undergo consid-
erable hepatic elimination, rendering their use less problematic in the patient
with reduced clearance. Some beta-blockers including acebutolol, atenolol,
betaxolol, and bisoprolol accumulate in renal patients and require dose adjust-
ment as well. - Spironolactone has been shown to be an effective adjunct in the patient with RH
[ 31 ]. Since primary aldosteronism forms up to 20% of cases of RH in some
series, spironolactone is an important and frequently used agent in these patients
[ 32 ]. However, when a patient has reduced GFR, the most dangerous adverse
effect of spironolactone emerges, hyperkalemia. Patients with stages 3–5 CKD
are prone to hyperkalemia; thus, addition of spironolactone to the antihyperten-
sive regimen of these patients increases the risk of life-threatening severe hyper-
kalemia [ 33 ]. When prescribed to the patient with GFR values >30 ml/min, close
follow-up is the rule. Type 2 diabetes mellitus and concomitant use of ACE
inhibitors or ARBs increase the risk of hyperkalemia further. GPs should closely
follow these patients and instruct them not to have a diet rich in fruit and vegeta-
bles. Same principles apply to the more specific aldosterone antagonist, eplere-
none, as well.
Y. S o l a k