Letter to the Editor

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Severe Paradoxical Hypertension With SBP DBP

Angiotensin-Converting Enzyme Inhibitors: 250
An Unusual Feature of Renal Artery Stenosis
To the Editor: 200
Angiotensin-converting enzyme (ACE) inhibitors are fre-

BP (mmHg)
quently used in the treatment of hypertension, heart failure, and 150
renal disease but may cause acute renal failure in patients with
renal artery stenosis (RAS).1 We describe a novel adverse effect 100
of ACE inhibitors in patients with advanced chronic kidney
disease (CKD) and RAS. 50
We observed 4 episodes of severe paradoxical hypertension in
3 patients with CKD (Table) and bilateral RAS, during initiation
or titration of the ACE inhibitor ramipril (Tritace, Sanofi-Aventis). 0
22:30 10:00 19:00 22:00 06:30
The etiology of CKD was atherosclerotic renovascular disease in
Time
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each case. Bilateral, hemodynamically significant RAS had been

demonstrated previously with both Doppler ultrasound and renal
angiography in all 3 of the patients and magnetic resonance
angiography in 2 patients. Blood pressure (BP) measurement using
an automated oscillometric device (Dinamap Pro series, GE
Healthcare) demonstrated initial transient hypotension or relative
hypotension, after administration of ramipril, followed by re-
bound severe hypertension (Figure 1). This phenomenon oc-
curred in patient 1 after increasing ramipril from 7.5 mg to 10.0
mg; in patient 2 with the addition of 10.0 mg of ramipril; and in
patient 3 with the addition of 5.0 mg of ramipril. Only patient 2
was taking an angiotensin receptor blocker. Cessation of ramipril
in each case resulted in lower BPs, with reduced requirements for
antihypertensive therapy (Figure 2). The phenomenon was recur-
rent in patient 1 when rechallenged with an ACE inhibitor. This
episode was complicated by hypertensive encephalopathy and a
generalized seizure, with a BP of 240/120 mm Hg. Two days
after the cessation of ramipril, the patients systolic BP ranged
from 120 to 130 mm Hg on a single antihypertensive.
Other causes for the worsening of hypertension were excluded.
The 2 patients on maintenance hemodialysis were considered to
be euvolemic on clinical examination. Review of dialysis records
in these patients did not reveal orders for extra ultrafiltration,
suggesting that they were not volume overloaded. The third
patient was weighed daily, and weight decreased by 1.2 kg over
several days after the initiation of ramipril, despite worsening
Figure 1. Representative BP recordings from patient 1, showing
initial fall in BP followed by a hypertensive surge. Ramipril (7.5
mg) was given at 8 AM. She was not on any other antihyperten-
sive therapy at the time. SBP indicates systolic BP; DBP, dia-
stolic BP.
remained constant during initiation or titration of ramipril, as did
the recombinant erythropoietin dose.
We describe severe hypertension apparently secondary to
ACE inhibitor therapy in the setting of bilateral RAS and CKD.
The mechanism is unclear, but we postulate that, in the setting of
fixed afferent obstruction, the additional drop in glomerular
pressure induced by ACE inhibitors led to activation of the
renin-angiotensin-aldosterone system with resulting rebound hy-
perreninemia and hypertension. This hypothesis might be sup-
ported by the measurement of plasma renin concentration during
an observed episode. It is interesting to note that ACE inhibitor
therapy precipitated simultaneous acute renal failure in patient 3.
This is thought to be mediated by the same process of reduced
SBP DBP
2 50
200
BP (mmHg)

hypertension. None of the patients received intravenous infusions

during the period of interest. Other antihypertensive medication 150

10 0
Table. Patient Characteristics
Patient Age Sex Renal Function 50

1 78 F ESRF on hemodialysis
0
2 episode 1 79 M ESRF on hemodialysis 1 2 3 4 5 6 7 8
Day
2 episode 2 79 M ESRF on hemodialysis
3 83 F CKD stage 4, eGFR 25 mL/min per 1.73 m2 Figure 2. Mean daily BP readings from patient 1. Systolic BP
worsened when the dose of ramipril was increased from 7.5 mg
ESRF indicates end-stage renal failure; F, female; M, male; eGFR, estimated to 10.0 mg on day 2, but control improved after it was stopped
glomerular filtration rate (calculated according to the 4-varible Modification of on day 7, without changing other antihypertensive therapy. SBP
Diet in Renal Disease formula2). indicates systolic BP; DBP, diastolic BP.

(Hypertension. 2009;54:e17-e18.)
2009 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.109.137745

e17
 e18 Hypertension September 2009

glomerular pressure. A similar effect might be expected with Edmond M. Cronin

angiotensin receptor blockers but not with other antihyperten- Sean F. Leavey
sives, because they lack a vasodilator effect on the efferent John Francis Walker
arteriole. Department of Nephrology
Severe paradoxical hypertension may be an adverse effect of Waterford Regional Hospital
ACE inhibitor therapy in the setting of RAS and CKD. Clinicians Waterford, Ireland
should be aware of this when treating patients with known or
suspected RAS. 1. Farrow PR, Wilkinson R. Reversible renal failure during treatment with
captopril. BMJ. 1979;1:1680.
2. Levey AS, Greene T, Kusek J, Beck G. A simplified equation to predict
Disclosures glomerular filtration rate from serum creatinine [abstract]. J Am Soc
None. Nephrol. 2000;11:155A.
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 Severe Paradoxical Hypertension With Angiotensin-Converting Enzyme Inhibitors: An
Unusual Feature of Renal Artery Stenosis
Edmond M. Cronin, Sean F. Leavey and John Francis Walker

Hypertension. 2009;54:e17-e18; originally published online July 27, 2009;

Downloaded from http://hyper.ahajournals.org/ by guest on March 11, 2017

doi: 10.1161/HYPERTENSIONAHA.109.137745
Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2009 American Heart Association, Inc. All rights reserved.
Print ISSN: 0194-911X. Online ISSN: 1524-4563

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