CASE STUDY

www.nature.com/clinicalpractice/neph

Adverse outcomes of renovascular hypertension

during pregnancy
Bjorg Thorsteinsdottir, Garvan C Kane, Michael J Hogan, William J Watson, Joseph P Grande
and Vesna D Garovic*
S U M M A RY
Background A 26-year-old primigravida, with no history of hypertension,

presented at 20 weeks of gestation with severe pre-eclampsia. A pelvic

ultrasound revealed intrauterine fetal death, probably caused by placental
abruption. The pregnancy was terminated by induction with oxytocin,
followed by a vaginal breech delivery. The patient remained hypertensive
for 8 weeks after delivery.
Investigations Physical examination, laboratory investigation, renal
angiogram and renal-vein renin sampling.
Diagnosis An atrophic right kidney secondary to an occluded right
renal artery, probably caused by dissected fibromuscular dysplasia;
a contralateral high-grade stenosis secondary to fibromuscular dysplasia.
Management Right nephrectomy and angioplasty of the left renal artery.
KEYWORDS hypertension, pre-eclampsia, pregnancy outcomes,
renal artery stenosis, renovascular hypertension

CME

B Thorsteinsdottir is a senior associate consultant in Community Internal

Medicine, Mayo Clinic, and Instructor in Medicine, Mayo Medical School,
Rochester, MN, USA. GC Kane is a fellow in Cardiovascular Diseases at Mayo
Clinic and Instructor in Medicine, Mayo Medical School, Rochester, MN,
USA. MJ Hogan is an attending physician in Regional International Medicine
and Program Director for Clinical Reviews at Mayo Clinic, Scottsdale, AZ,
USA. WJ Watson is Chief of the Division of Maternal and Fetal Medicine,
Mayo Clinic and Professor in Obstetrics and Gynecology, Mayo Medical
School, Rochester, MN, USA. JP Grande is Professor in Laboratory Medicine
and Pathology and Associate Dean for Academic Affairs, Mayo Medical
School, Rochester, MN, USA. VD Garovic is an attending physician in
Nephrology and Hypertension at Mayo Clinic and Assistant Professor of
Medicine, Mayo Medical School, Rochester, MN, USA.
Correspondence
*Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester,
MN 55905, USA
garovic.vesna@mayo.edu
Received 16 April 2006 Accepted 28 July 2006
www.nature.com/clinicalpractice
doi:10.1038/ncpneph0310

NOVEMBER 2006 VOL 2 NO 11

This article offers the opportunity to earn one

Category 1 credit toward the AMA Physicians
Recognition Award.
THE CASE

A 26-year-old primigravida was transferred to

our institution at 20 weeks of gestation for an
emergency delivery following placental abruption and intrauterine fetal demise. The vaginal
bleeding had prompted admission to another
hospital 4 days earlier. She had had an otherwise
uneventful pregnancy and she had no history of
hypertension (blood pressure was 120/66 mmHg
2 weeks before admission). Upon admission,
her blood pressure was 207/104 mmHg and her
predicted 24 h protein excretion, as determined by
the protein-to-osmolality ratio in a random urine
specimen, was 1.1 g. Her kidney function was
normal with a blood urea nitrogen (BUN) level
of 7.85 mmol/l and a serum creatinine concentration of 70.72 mol/l (0.8 mg/dl). Laboratory
evaluation revealed a decreased hemoglobin
concentration (106 g/l), low platelet count
(79 109/l), and an elevated serum aspartate
aminotransferase level, which peaked at 79 U/l.
Clinical and laboratory findings were consistent
with severe pre-eclampsia and possibly HELLP
syndrome (hemolysis, elevated liver enzymes, and
low platelet count). The patient received two doses
of 5 mg hydralazine hydrochloride intravenously.
Oxytocin was given as a continuous infusion, and
the dose varied from 2 U/h to 10 U/ h over the
course of 8 h, which resulted in the breech delivery
of a 260 g stillborn male infant. Her predicted 24 h
protein excretion decreased to 369 mg within the
first week after delivery, but she remained hypertensive, with systolic blood pressures ranging
between 130 mmHg and 170 mmHg, and was
treated with labetalol hydrochloride, 200 mg
twice daily.
Six weeks postpartum, the patients hypertension persisted and her blood pressure
regimen was changed to amlodipine 5 mg twice
daily, atenolol 50 mg once daily, and doxazosin
2 mg daily. Physical examination revealed a

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Figure 1 Renal arteriograms with contrast showing (A) occluded right renal artery, (B) fibromuscular
dysplasia of the middle left renal artery and (C) successful treatment with angioplasty.

Figure 2 Histology of the surgically removed right

kidney showing: ischemic wrinkling and thickening
of the glomerular basement membrane with
mild mesangial matrix expansion (white arrow);
thickening of the tubular basement membranes
(black arrow) with patchy lymphocytic interstitial
infiltrate. Hematoxylin and eosin stain; original
magnification 100.

continuous systolicdiastolic bruit in the periumbilical area. Despite the three-drug regimen,
her hypertension was inadequately controlled,
with systolic pressures of 174190 mmHg and
diastolic pressures of 94106 mmHg. Renal
artery stenosis was suspected. A renal angiogram
showed an occluded right renal artery with an
atrophic right kidney (Figure 1A), measuring
approximately 7 cm along its length; the left
kidney measured 11.2 cm along its length, with
evidence of fibromuscular dysplasia in the midportion of the left renal artery (Figure 1B).
Renal-vein renin measurements1 showed a
right renal-vein renin activity of 545.10 pmol/l/h
versus a left renal-vein renin activity of
35.55 pmol/l/h with a ratio of 15.3, lateralizing

652 NATURE CLINICAL PRACTICE NEPHROLOGY

to the right, atrophic kidney. The right kidney

was removed surgically. Histological findings
were consistent with ischemic nephropathy
(Figure 2). The patient tolerated the procedure
well and her blood pressure improved, averaging
130/80 mmHg on the same three-drug regimen.
Two months later, she underwent a left renal
artery angioplasty (Figure 1C), after which her
blood pressure normalized without medication
and her 24 h urine collection showed no significant proteinuria (54 mg/24 h). One year later, the
patient remained normotensive and delivered a
healthy infant after an uneventful pregnancy.
DISCUSSION OF DIAGNOSIS
Initial diagnosis

Pre-eclampsia is a pregnancy-specific disorder,

clinically characterized by hypertension (blood
pressure 140/90 mmHg) and proteinuria
(300 mg in a 24 h urine collection).2 The condition affects both women who were normotensive
before their pregnancies (pure pre-eclampsia)
and those with a history of chronic hypertension,
defined as a blood pressure 140/90 mmHg
before pregnancy or before the 20th week of
gestation. Chronic hypertension can also occur
for the first time during pregnancy. In these
women, hypertension develops for the first time
during the second half of pregnancy as gestational hypertension; subsequent failure of blood
pressure to normalize by 12 weeks postpartum
leads to the diagnosis of chronic hypertension.
Compared with normotensive pregnant
women, the risk of developing pre-eclampsia
is significantly higher in women with a history
of chronic hypertension, affecting 25% of
these patients (superimposed pre-eclampsia).3
Chronic hypertension is most commonly

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essential in origin, although up to 5% of these

patients may have secondary forms (i.e. hypertension with identifiable underlying causes).4
As pure pre-eclampsia typically occurs later in
pregnancyoften well into the third trimester
a diagnosis of secondary hypertension needs to
be considered in women who develop severe
forms of pre-eclampsia in the second trimester.
Renovascular hypertension is a form of
secondary hypertension that occurs as a result
of critical narrowing of the renal arteries, most
commonly caused by atherosclerotic disease or
fibromuscular dysplasia. Narrowing of the renal
arteries leads to renal hypoperfusion and activation of the reninangiotensinaldosterone
system, which has a central role in the development of hypertension. Renal artery stenosis
secondary to fibromuscular dysplasia commonly
affects women of childbearing age and thus
remains an important consideration as a cause
of secondary hypertension during pregnancy.
The prevalence of renovascular hypertension in
women of childbearing age has not been determined, however. Published data are limited to
case reports and small series with total numbers
of patients not exceeding 30; nevertheless,
the data do indicate that among patients with
chronic hypertension, those with renovascular
hypertension might be at an even higher risk of
earlier and more-severe pre-eclampsia than those
with essential hypertension.5
The patient in this case presented with severe
early pre-eclampsia, but did not have a history
of hypertension before pregnancy. Her blood
pressure failed to normalize after delivery,
leading to the diagnosis of chronic hypertension.
The failure of three antihypertensive drugs
to control her blood pressure, and the loud
abdominal bruit, indicated a possible diagnosis
of renovascular hypertension.
Clinical features of renovascular hypertension
in pregnancy
In hemodynamic studies of several hundred
hypertensive pregnant patients, a patient with
known renal artery stenosis had the highest
elevation of peripheral vascular resistance,
exceeding even the resistances measured in two
patients with pheochromocytoma.6 Conceivably,
significant fluid retention in the third trimester,
which occurs in the setting of elevated peripheral vascular resistance, might exacerbate
hypertension and related complications as the
pregnancy approaches full term.

The patient presented here developed severe

pre-eclampsia early in pregnancy; the preeclampsia was further complicated by placental
abruption and intrauterine fetal demise. The
severity of her hypertension and the physical
findings indicated renovascular hypertension,
prompting further diagnostic studies. Given
our patients high pre-test probability for renal
artery stenosis, we decided to proceed directly
to angiography. We reasoned that results of
a noninvasive test (such as captopril renography, duplex sonography, magnetic resonance angiography or computed tomographic
angiography) would not change our decision,
and that we would have pursued an angiogram irrespective of the results of noninvasive
testing. An angiogram revealed bilateral renal
artery stenosis secondary to fibromuscular
dysplasia, with complete occlusion of the right
artery, resulting in right kidney atrophy, and a
high-grade left renal artery stenosis.
Careful review of published case series
and case reports and the experience at our
institution (Table 1) revealed that those with
unrecognized renal artery stenosis typically
present with either accelerated hypertension
or early and/or severe pre-eclampsia (Table 2).
As in previous reports, our case series indicates
that women with renovascular hypertension are
at particularly high risk of fetal and maternal
complications. Two women experienced
second-trimester pregnancy losses secondary
to intrauterine fetal demise, and one pregnancy
was electively terminated because of possible
teratogenic fetal effects after exposure to radiation and contrast during a renal angiogram
performed early in pregnancy. One woman
underwent early induction because of severe
pre-eclampsia, and only one carried her pregnancy to full term while on antihypertensive
medications.
Because of the retrospective character of our
study, a selection bias might exist for patients
with severe hypertension in whom particularly
poor pregnancy outcomes led to further investigations and correct diagnoses. Conceivably, a
significant proportion of patients with renovascular hypertension might have their blood
pressure controlled effectively using medications
and they might do fairly well throughout pregnancy.6 We were unable to identify any prospective studies examining the prevalence, natural
course, and prognosis of renal artery stenosis in
pregnant patients, however.

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Table 1 Case series of clinical presentations and pregnancy outcomes in patients with renovascular hypertension.a
Patient

Presentation

Pregnancy
outcome

Renal angiogram

Treatment

Subsequent
pregnancies

Index
case

Severe pre-eclampsia,
placental abruption at
gestational week 20

Labor induction for

intrauterine fetal
demise

Revealed occluded
right renal artery, and
fibromuscular dysplasia
of left renal artery

Nephrectomy of the
atrophic right kidney
and left renal artery
angioplasty

One normotensive,
uneventful
pregnancy

#1

Hypertensive crisis at
gestational week 5;
abdominal bruit

Elective abortion
after renal
angiogram

Revealed bilateral
fibromuscular dysplasia at
gestational week 6

Bilateral angioplasty
resulting in cure of
hypertension

Two normal, fullterm pregnancies

#2

Severe hypertension at
gestational week 23

Hospitalized at
gestational week 23
for blood-pressure
control; carried to
full term

Performed 4 years after

delivery because of
resistant hypertension;
revealed right fibromuscular
dysplasia

Medical therapy

None

#3

Pre-eclampsia with
second pregnancy; blood
pressure failed to normalize
postpartum

Early induction at
gestational week 36

Performed 9 years after

delivery because of
resistant hypertension;
revealed right fibromuscular
dysplasia

Angioplasty with
improved bloodpressure control

None

#4

Chronic hypertension after

pre-eclampsia with third
pregnancy; presented with
hypertensive urgency at
gestational week 17 of her
fourth pregnancy

Intrauterine fetal
demise

Revealed bilateral
fibromuscular dysplasia
2 months after delivery

Bilateral angioplasty
with cure of
hypertension

None

aRetrospective

review of all women of childbearing age diagnosed with hypertension and renal artery stenosis at Mayo Clinic, Rochester from 19862005;
approved by the Institutional Review Board.

DISCUSSION OF TREATMENT
Before conception or after an unsuccessful
pregnancy

The introduction of angiotensin-convertingenzyme (ACE) inhibitors and angiotensin

II receptor blockers has resulted in marked
improvement in blood-pressure control in
patients with renovascular hypertension. Special
attention should be given to women of childbearing age who have been treated with these
antihypertensive medications prior to conception.
Both ACE inhibitors and angiotensin II receptor
blockers are contraindicated during pregnancy
and are therefore commonly discontinued during
prepregnancy counseling. Difficulty in controlling blood pressure with alternative regimens
should raise suspicion of and prompt evaluation
for renovascular causes. Once the diagnosis is
confirmed, and if revascularization is considered,
conventional percutaneous contrast angiography
with angioplasty remains the gold standard for
treatment of fibromuscular dysplasia. In young
patients with such a diagnosis who typically
present with hypertension of a short duration,
successful revascularization might be curative.7
In fibromuscular dysplasia, progression
to total occlusion might occur, although it is

654 NATURE CLINICAL PRACTICE NEPHROLOGY

relatively uncommon. In our series of 74 patients

(43 females, 31 males, mean age 65 years) who
underwent nephrectomy of an atrophic kidney
for uncontrolled hypertension, 8 patients (11%)
had fibromuscular dysplasia.8 Preoperative assessment of the whole cohort indicated a significant
decrease in size of the affected kidney (mean
length 8.1 cm) and poor function, with an average
contribution of only 12% to overall renal function,
as assessed by nuclear renogram. After nephrectomy, blood-pressure control improved in 58 of
these patients (79%), with improvement defined
either as a cure (n = 10) or as a reduction in mean
arterial pressure of >10 mmHg while taking fewer
antihypertensive medications (n = 48). There was
no significant change in glomerular filtration rate
from pre-nephrectomy to a 1-year follow-up visit
(mean change 0.2 ml/min). Our results indicate
that in selected patients with resistant hypertension and renal artery disease, nephrectomy of
a small, poorly functioning kidney can improve
blood-pressure control without further loss of
renal function.
In the patient presented in this case, renal-vein
renin measurements lateralized to the right kidney,
which, not amenable to revascularization because
of advanced atrophy, was removed surgically.

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Table 2 Clinical presentations of renovascular hypertension during pregnancy.

Clinical presentation

References

Examples of cases
(see Table 1)

Severe hypertension and pre-eclampsia early in

pregnancy (i.e. during the first or second trimester)
in previously normotensive women

Easterling et al. (1991)6

Pollock et al. (1990)14
Cohen et al. (2005)15

Index case and

cases #1 and #2

Pre-eclampsia in previously normotensive women with

failure of blood pressure to normalize after delivery,
especially in patients with clinical signs and symptoms
suggestive of renovascular hypertension19

Wylie et al. (1960)18

Case #3

Accelerated hypertension or early and/or severe

superimposed pre-eclampsia in women with prior history
of chronic hypertension

Hennessy et al. (1997)5

Heyborne et al. (1991)11
Le et al. (1995)12
Landesman et al. (1961)19

Case #4

Recurrent pre-eclampsia

Koskela and Kaski (1971)20

Of note, lateralizing renins, as manifested

by a ratio of 1.5, are considered diagnostic
for hemodynamically significant renal artery
stenosis and predictive of surgical curability.1
Initial improvement in blood-pressure control
after nephrectomy was followed by successful
revascularization of the contralateral kidney and
subsequent cure of hypertension.
While the literature clearly documents poor
pregnancy outcomes in women with renovascular hypertension, only two studies have
reported pregnancy outcomes after repair of
renal artery stenosis. Sellars et al. reported four
patients with renovascular hypertension, two of
whom had had unsuccessful pregnancies before
intervention for renal artery stenosis. After
successful revascularization, the four women
had four uncomplicated pregnancies and two
pregnancies with mild gestational hypertension
between them.9 Another study reported the
case of a woman who underwent nephrectomy
for advanced fibromuscular dysplasia but had
a subsequent pregnancy resulting in stillborn
twins; the still births were unrelated to hypertension, however, as she remained normotensive
throughout her pregnancy and delivery.10 In the
patient presented here, and in patient #1 from
our case series (Table 1), normalization of blood
pressure after interventions were followed by
uncomplicated pregnancies and deliveries of
healthy infants.
During pregnancy

Medical treatment of hypertension during

pregnancy remains a therapeutic challenge.
It is frequently suboptimal, as ACE inhibitors
and angiotensin II receptor blockers are

contraindicated. Isolated case reports have

addressed the use of renal angiograms and revascularization for the diagnosis and treatment of
renovascular hypertension during pregnancy,
for accelerated hypertension refractory to drug
therapy.6,1115 By limiting the radiation exposure to less than 5 rad (i.e. 50 mGy), the probability of deleterious fetal effects is small16 and
outweighed by the benefit of improved bloodpressure control, which allows the pregnancy
to be carried closer to term and reduces the
morbidity and mortality associated with preterm
deliveries. With respect to surgical revascularization, it is important to recognize that bypass
techniques that involve cross-clamping of the
aorta are contraindicated in pregnancy.11
CONCLUSION

Given the reported severity of complications of

renovascular hypertension in pregnancy, it seems
justified to exclude renovascular disease in young
hypertensive women before conception, especially in those with clinical features suggestive of
secondary hypertension.17 This condition should
also be considered in patients who present with
accelerated hypertension or severe pre-eclampsia,
particularly if it occurs early in pregnancy or if
there is a history of two or more affected pregnancies. Nephrectomy of a small, poorly functioning kidney and/or revascularization after
an unsuccessful pregnancy can improve both
maternal and fetal outcomes in subsequent pregnancies. Based on a few published reports, revascularization can be performed safely even during
pregnancy, assuming that appropriate shielding is
implemented and the dose of radiation is limited
to less than 5 rad.

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Competing interests
The authors declared
they have no competing
interests.

References
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