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a first-dose hypotensive reaction. They are useful in CKD patients with RH, as well
as in those with symptoms of prostatic hypertrophy. Vasodilatation can lead to
peripheral edema, so they are commonly combined with diuretics. Alpha-blockers
do not require dose modification in CKD, since they are excreted via the liver [ 24 ].
Direct Vasodilators
Hydralazine and minoxidil both act by directly causing vascular smooth-muscle
relaxation and vasodilatation. Hydralazine is rarely used in CKD. Minoxidil is some-
times indicated in patients with RH; however, its side effects limit its use to the most
resistant cases. Because of fluid retention and tachycardia, these drugs (especially
minoxidil) are usually combined with a BB and a loop diuretic. Hydralazine and min-
oxidil do not require dose adjustment in patients with impaired kidney function [ 24 ].
Treatment of RH in Dialysis-Dependent (CKD-5D) Patients
In patients who are receiving renal replacement therapy, specific BP targets derived
from RCTs are lacking. The National Kidney Foundation Kidney Disease Outcomes
Quality Initiative (KDOQI) guidelines suggest that pre-hemodialysis (HD) and
post-HD BP should be 140/90 mmHg and 130/80 mmHg, respectively, but these
targets are mainly based on the expert judgment of the working group, applying
weak evidence [ 48 , 49 ].
ACEIs and ARBs
The KDOQI guidelines suggest RAS inhibitors to be the preferred antihypertensive agents
in dialysis patients, particularly in those with diabetes or a history of heart failure [ 49 ].
Several studies demonstrated a 5–12 mmHg reduction in systolic BP with ACEIs
[ 50 , 51 ]. Retrospective analyses and small clinical trials also suggest that ACEIs
may help preserve residual renal function [ 52 ], decrease arterial stiffness [ 50 ] and
left ventricular hypertrophy [ 53 ], reduce mortality after acute coronary syndromes
[ 54 ], and improve overall survival [ 55 , 56 ] in HD patients. In the Fosinopril in
Dialysis (FOSIDIAL) trial [ 51 ], 397 HD patients with left ventricular (LV) hyper-
trophy were randomized to fosinopril or placebo and followed for 2 years. The pri-
mary outcome was a combined endpoint of cardiovascular death, nonfatal
myocardial infarction, unstable angina, stroke, cardiovascular revascularization,
hospitalization for heart failure, and resuscitated cardiac arrest. At the end of the
study, there was a nonsignificant reduction in the primary endpoint with fosinopril.
Some studies found ACEIs to be relatively safe in dialysis patients, with no sig-
nificant effect on serum potassium, while others suggested that ACEIs may increase
L. Segall