14 CME REVIEW ARTICLE Volume 74, Number 5

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright © 2019 Wolters Kluwer Health,
Inc. All rights reserved.

CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total of
36 AMA PRA Category 1 Credits™ can be earned in 2019. Instructions for how CME credits can be earned appear on the last page
of the Table of Contents.

Update on the Prenatal Diagnosis and

Outcomes of Fetal Bilateral Renal Agenesis
Carola Huber, MS,*† Sherif A. Shazly, MBBCh, MS,‡ Yair J. Blumenfeld, MD,§
Eric Jelin, MD,k and Rodrigo Ruano, MD, PhD}
*Medical Student, Medical University of Graz, Graz, Austria; †Research Trainee, and ‡Resident in Obstetrics and Gynecology,
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN; §Associate Professor and Director of Fetal Therapy,
Division of Maternal-Fetal Medicine and Obstetrics, Department of Obstetrics and Gynecology, Stanford University School of
Medicine, Stanford, CA; kAssistant Professor and Director of Johns Hopkins Children's Center Fetal Program, Division of Pediatric
Surgery, The Johns Hopkins Hospital, Baltimore, MD; and }Professor of Obstetrics & Gynecology, Pediatrics and Physiology &
Biomedical Engineering, Chair of the Division of Maternal-Fetal Medicine, and Director of Mayo Clinic Fetal Section, Department of
Obstetrics and Gynecology, Mayo Clinic, Rochester, MN

Importance: Bilateral renal agenesis is a rare congenital anomaly associated with poor prognosis.
Objective: The aims of this article are to review and summarize evidence on prenatal diagnosis and outcomes
of bilateral renal agenesis.
Evidence Acquisition: A search was undertaken using PubMed and ClinicalTrials.gov databases from
January 1, 1998, to September 1, 2018. Search terms include “prenatal diagnosis” OR “outcomes” AND “bilateral
renal agenesis.” Search was limited to English language.
Results: Fetal ultrasonography is the primary imaging modality for prenatal diagnosis of fetal urogenital tract
abnormalities. However, ultrasonography is limited by several factors; it is operator dependent and associated
with small field of view, has limited soft-tissue acoustic contrast, and is also influenced by patient habitus and
fetal position. Color Doppler ultrasonography can be used as an adjunct to exclude bilateral renal agenesis by
visualizing renal arteries. In the literature, prenatal magnetic resonance imaging has been reported to be equal
to or superior to prenatal ultrasonography. Bilateral renal agenesis with oligohydramnios/anhydramnios is asso-
ciated with a poor prognosis; perinatal death occurs secondary to pulmonary hypoplasia in the majority of cases.
Conclusions: Ultrasonography in combination with color Doppler ultrasonography permits the fetal urinary
tract to be assessed in the first and early second trimester of gestation. The magnetic resonance imaging can
be used as a complementary adjunctive modality in equivocal or inconclusive ultrasonographic findings.
Target Audience: Obstetricians and gynecologists, family physicians.
Learning Objectives: After completing this activity, the learner should be able to describe the natural history of fe-
tuses with bilateral renal agenesis; explain to patients the accuracy and limitations of the prenatal diagnosis of the
anomaly; and counsel patients regarding the perinatal outcome and prognosis of fetuses with this condition.

Bilateral renal agenesis, defined as congenital ab-

All authors, faculty, and staff in a position to control the content of this
CME activity and their spouses/life partners (if any) have disclosed that
they have no financial relationships with, or financial interests in, any com-
mercial organizations relevant to this educational activity.
The publication is approved by all authors and the responsible
authorities of our hospital.
Correspondence requests to: Rodrigo Ruano, MD, PhD, Division of
Maternal-Fetal Medicine, Department of Obstetrics and Gynecology,
Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905.
E-mail: ruano.rodrigo@mayo.edu; rodrigoruano@hotmail.com.
www.obgynsurvey.com | 298
sence of both kidneys, complicates approximately 1 in
every 3000 pregnancies.1,2 Renal agenesis results from
failure of ureteric buds to either form or reach the meta-
nephric mesenchyme with subsequent apoptosis.3 Bi-
lateral renal agenesis typically presents with absence
of fetal kidneys, oligohydramnios, and fetal deforma-
tions, described as the Potter sequence, including fat-
tened facies, limb malformations, low-set abnormal

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 Fetal Bilateral Renal Agenesis • CME Review Article
ears, and pulmonary hypoplasia.3,4 If bilateral renal
agenesis is suspected, a detailed prenatal anatomy scan
is warranted to identify renal anomalies, exclude other
associated structural abnormalities, and assess renal
tract architecture and amniotic fluid volume for subse-
quent monitoring.5
Bilateral renal agenesis is associated with a high neo-
natal mortality rate and a poor prognosis, as severe oli-
gohydramnios and pulmonary hypoplasia are generally
incompatible with survival. Only 3 case reports describe
survival of singletons with bilateral renal agenesis and
normal pulmonary function; in 2, survival occurred fol-
lowing in-utero therapy (serial amnioinfusions), whereas
the other report lacked prenatal data regarding amniotic
fluid volume at midtrimester.1,4,6,7 A few case reports
depict monoamniotic twin pregnancies with 1 fetus
having normal renal function and 1 fetus with bilateral
renal agenesis who survived because of the normal urine
production from the cotwin.7 Importantly, there are no
reported survivors of prenatally diagnosed singletons
with bilateral renal agenesis without fetal intervention.
Prenatal diagnosis of bilateral renal agenesis using ul-
trasonography, color Doppler ultrasonography, and
magnetic resonance imaging (MRI) has been reported
in the literature.5,8–10 Currently, standard practice for di-
agnosis of renal anomalies is via second-trimester anat-
omy scan.11,12 However, diagnosis can still be mistaken
because of ultrasound limitations. In this review, we
aim to assess the value of different screening modalities
as well as clinical outcomes of bilateral renal agenesis.
To meet these objectives, a search was conducted
using PubMed and ClinicalTrials.gov databases from
January 1, 1998, to September 1, 2018, using the follow-
ing search terms: “prenatal diagnosis” OR “outcomes”
AND “bilateral renal agenesis.” Only studies in English
were included. Sample size was not a basis for exclusion,
and all study types including case reports were consid-
ered in this review. Studies that assess other fetal urinary
tract anomalies or do not specify bilateral renal agenesis
in their analysis were excluded.
PRENATAL DIAGNOSIS
Prenatal Ultrasonography
Prenatal ultrasonography is the primary imaging
modality for assessment of fetal urogenital tract abnor-
malities.5,13,14 Ultrasonography is safe for fetus and
mother, is relatively inexpensive, enables real-time im-
aging, and is readily available.13,15,16 Using ultraso-
nography, normal kidneys may be visible as early as
9 weeks of gestation. Kidneys should be visualized
by ultrasonography in 80% of the cases at 11 weeks
and in 92% of cases at 13 weeks of pregnancy.3,11,12
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
299
Absence of fetal kidneys in the renal fossa, an
empty bladder, and the presence of anhydramnios af-
ter 16 weeks gestation are strong indicators of bilat-
eral renal agenesis.12 Although anhydramnios is a
critical feature of bilateral renal agenesis early in the
second trimester, it generally cannot be detected prior
to 16 weeks' gestation. This is attributed to the fact
that fetal urine production starts between 8 and 10 weeks
of gestation and does not contribute significantly to am-
niotic fluid volume until 16 weeks of gestation.3 Prior
to this gestational age, amniotic fluid is mainly formed
by secretions of the placenta, fetal membranes, and
skin.11,12 Once anhydramnios is present, visualization
of the fetal urinary tract and diagnosis of other fetal
anomalies with ultrasound are impaired.2,12
Prenatal ultrasonography has other limitations that
may adversely impact visualization of the kidneys.16,17
The fact that fetal kidneys appear echogenic early in
pregnancy makes it difficult to differentiate them from
adjacent structures.11 Adrenal glands may also be con-
fused with hypoplastic renal tissue.12 In addition, ultra-
sonography is operator dependent, provides a small
field of view, has limited soft-tissue acoustic contrast,
and is affected by beam attenuation from adipose tissue
and obscuration of portions of fetal anatomy by rever-
beration artifacts of the bony skeleton.5,8,12 Grandjean
et al18 reported that the sensitivity of a systematic ultra-
sonographic examination of the fetus between 18 and
22 weeks' gestational age to diagnose bilateral renal
agenesis was 83.7% in a series of cases with a postna-
tally confirmed diagnosis.
Doppler Studies
Color Doppler ultrasonography can be used as an ad-
junct for diagnosis of bilateral renal agenesis.11 Normal
fetal renal arteries should be seen as direct branches of
the abdominal aorta in posterior coronal view, just infe-
rior to the origin of the superior mesenteric artery.19
(Fig. 1A) Absence of renal arteries is highly suggestive
of bilateral renal agenesis11 (Fig. 1B).
Prenatal MRI
Magnetic resonance imaging examination of a human
fetus was first described in 1983.17 Since then, fetal
MRI has been increasingly involved as a valuable ad-
junctive technique for fetal imaging given the limita-
tions of ultrasonography screening.5,8,12,14 Magnetic
resonance imaging is limited by cost and is contraindi-
cated in individuals with claustrophobia or with metal-
lic prostheses. One common indication for fetal MRI is
evaluation of oligohydramnios and anhydramnios.17
Magnetic resonance imaging has also a good reliability
300 Obstetrical and Gynecological Survey

FIG. 1. A, Two-dimensional color Doppler of bilateral renal arteries in a coronal view of a healthy fetus at 20 weeks. B, Two-dimensional color
Doppler of bilateral renal arteries in a coronal view of a fetus with bilateral renal agenesis at 21 weeks.

and validity to quantify fetal pulmonary hypoplasia
with a high accuracy in assessing lung volumes.20,21
As pulmonary hypoplasia is associated with bilateral re-
nal agenesis, prenatal MRI lung measurement may be
helpful to assist counseling.
Fetal MRI has substantially advanced with the devel-
opment of heavily T2-weighted fast acquisitions pulse
sequences.22 Magnetic resonance imaging sequences
allow evaluation of fetal anatomy without the need for
maternal sedation. Furthermore, it enables the fetus to
be viewed in multiple planes with high resolution re-
gardless of fetal lie.5 Magnetic resonance imaging has
not been reported to cause harmful effects to the fetus,
even when employing high magnetic fields that allow
good soft tissue contrast with wide visual field.8,15
The development of faster imaging sequences has re-
duced artifacts caused by fetal movements, which pre-
viously degraded imaging quality.15,16 As there are
existing concerns about safety of gadolinium-based
contrast media in pregnancy, fetal MRI is performed
without the use of contrast agents.15
In a study, Hawkins et al23 reported that all pregnan-
cies with lethal fetal renal anomalies caused by renal
agenesis, multicystic dysplastic kidneys, or autosomal
recessive polycystic kidney disease were characterized
by the absence of the normal bright signal (signal void)
within renal pelvis and bladder on T2-weighted MRI.
Compared with ultrasonography, Alamo et al16 did
not appreciate significant difference between prenatal
ultrasonography and MRI findings in cases of bilateral
renal agenesis. However, MRI was superior to ultraso-
nography in unilateral renal agenesis in visualizing the
existing kidney in 2 cases. Also, Behairy et al13 reported
that MRI had no significant advantage over ultraso-
nography in cases of bilateral renal agenesis, which
may be attributed to the presence of oligohydramnios/
anhydramnios and the use of color Doppler to detect re-
nal arteries. Magnetic resonance imaging was utilized
to confirm the diagnosis. Said et al14 and Gupta et al10
found that both prenatal ultrasonography and fetal MRI
correctly diagnosed bilateral renal agenesis and were
consistent with postnatal findings. These prenatal imag-
ing studies supported parents' decision to terminate
pregnancy.14 However, MRI enabled better visualiza-
tion of fetuses with bilateral renal agenesis and severe
oligohydramnios.10
In contrast, Bazeed et al8 showed that fetal MRI and
prenatal ultrasonography were 73.5% concordant in di-
agnosing bilateral renal agenesis, and the diagnosis was
modified in 17.6% cases based on fetal MRI; the diag-
nosis was changed from inconclusive to bilateral or uni-
lateral renal agenesis in 8.8% of cases based on MRI
findings. Abdelazim and Belal5 concluded that fetal
MRI accuracy is slightly superior to ultrasonography
(accuracy is 89.5% vs 85.0%, respectively).
Multifetal gestation seems to impact accuracy of both
fetal MRI and prenatal ultrasonography. Sgro et al12 re-
ported false-positive diagnosis of bilateral renal agene-
sis in a twin pregnancy with anhydramnios based on
fetal MRI. However, postnatal follow-up revealed that
one twin had a small unilateral kidney that was not vi-
sualized either by prenatal ultrasonography or fetal
MRI. The other twin had bilateral renal agenesis and
died because of pulmonary hypoplasia. In conclusion,
although fetal MRI does not seem to be necessary for
diagnosis of bilateral renal agenesis, it may be indicated
if prenatal ultrasonography is limited by severely de-
creased amniotic fluid volume or fetal position.22,23 In
addition, postnatal or postmortem examination is con-
sidered important for confirmation of diagnosis and

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 Fetal Bilateral Renal Agenesis • CME Review Article
for quality control of ultrasonography and MRI in fetal
diagnosis.2
PROGNOSIS AND OUTCOME
Prenatally diagnosed bilateral renal agenesis is asso-
ciated with 100% lethality without prenatal therapy.
The major determinant of postnatal mortality is pul-
monary hypoplasia, which develops secondary to
anhydramnios.3 Behairy et al13 reported outcomes of
3 cases diagnosed with bilateral renal agenesis; 2 preg-
nancies were terminated at weeks 18 and 20 of gesta-
tion, and 1 fetus was delivered at week 22 and died
on postnatal day 3 because of pulmonary hypoplasia.
Gupta et al10 described 2 cases of bilateral renal agen-
esis and oligohydramnios; both cases did not survive.
Alamo et al16 reported 3 cases of bilateral renal agen-
esis: 2 pregnancies were terminated at 26 weeks of
gestation, and 1 died perinatally at 34 weeks of gesta-
tion. Geca et al17 presented a case of bilateral renal
agenesis diagnosed at week 26 of gestation that was
delivered vaginally after spontaneous onset of labor
at 34 weeks of gestation. Apgar scores were 6 and
4 at 1 and 5 minutes, respectively. However, the new-
born died 1 hour after delivery. On the other hand,
George et al4 described a case of a newborn with bilat-
eral renal agenesis and normal pulmonary function,
who did well on peritoneal dialysis while awaiting re-
nal transplant until the age of 4 years, but there was no
information related to the prenatal diagnosis and if the
fetal kidneys were possibly present earlier in the preg-
nancy (renal infarction). Unfortunately, the child died,
and full autopsy failed to reveal a definite cause of
death, although this was thought to be related to car-
diac arrest secondary to electrolyte imbalance.
Unlike singleton pregnancies, there have been few
case reports of bilateral renal agenesis with normal pul-
monary function in monoamniotic twins. This may be
attributed to the higher false-positive rate with either
ultrasonography or MRI compared with singleton
pregnancies. As previously mentioned, Sgro et al12 re-
ported survival of 1 twin that was misdiagnosed with
bilateral renal agenesis. The twin who survived had a
unilateral hypoplastic kidney that was not visualized
prenatally. Perez-Brayfield et al7 depicted a case report
of a monoamniotic twin born discordant for bilateral
renal agenesis with normal pulmonary function be-
cause of the normal urine production of the cotwin.
The prenatal ultrasonography scan revealed no abnor-
malities until delivery at 35 weeks of gestation. After
bilateral renal agenesis was diagnosed for 1 twin due
to renal failure, peritoneal dialysis was started. The
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
301
newborn died at 2 months because of complications
from the peritoneal dialysis.
Although these cases are typically managed conser-
vatively, Bienstock et al1 reported a unique case of bi-
lateral renal agenesis with anhydramnios that was
diagnosed at 23 1/7 weeks of gestation and underwent
serial amnioinfusion. Serial amnioinfusion was per-
formed as an experimental therapy to enhance lung de-
velopment and avoid pulmonary hypoplasia. After
delivery, the newborn had excellent respiratory effort
with appropriate lung volumes, and peritoneal dialysis
was initiated at 36 hours of life. The newborn was
9 months old at the time of the case report and was on
daily home peritoneal dialysis awaiting renal transplan-
tation at 12 to 24 months of age.
In summary, there are very few cases of fetuses sur-
viving bilateral renal agenesis, and no cases without
fetal therapy have been reported in which the prenatal
diagnosis was made at the time of midtrimester anatomy
survey, and there was known to be long-standing oligo-
hydramnios. As the presence of amniotic fluid is vital to
lung development,24 there is a very poor prognosis at-
tributed to pulmonary hypoplasia.4,5,11 Thus, the use of
serial amnioinfusion may present an option to improve
survival. However, further studies are warranted to eval-
uate the risks and benefits of this approach.
A multicenter study has begun at Mayo Clinic and
Johns Hopkins Hospital, with the support from North
American Fetal Therapy Network (ClinicaTrials.gov
identifier NCT03723564 and ClinicalTrials.gov identi-
fier NCT03101891). The main goals of these trials are
to determine the safety, feasibility, and efficacy of serial
amnioinfusion to treat isolated bilateral renal agenesis
diagnosed before 26 weeks of gestation. The design of
the clinical trial was, in part, a byproduct of an extensive
multidisciplinary national ethics conference that took
into account (1) potential risks and benefits, (2) clinical
care compared with innovation compared with research,
(3) counseling of expectant parents, (4) consent, (5) out-
come measures, (6) access and justice, (7) conflicts of in-
terest, (8) effects on clinicians, (9) effects on institutions,
and (10) long-term societal implications.25
CONCLUSIONS
Bilateral renal agenesis can be diagnosed prenatally.
Diagnostic criteria include absence of fetal kidneys,
oligohydramnios, and absent fetal bladder. Diagnosis
should be made as early as possible to facilitate patient
counseling and safe termination of pregnancy or enroll-
ment in a clinical trial of serial amnioinfusion. Although
prenatal ultrasonography is the primary diagnostic tool
of fetal anomalies, MRI can be helpful in some cases if
302 Obstetrical and Gynecological Survey
visualization is unsatisfactory secondary to oligohy-
dramnios or fetal lie. Color Doppler ultrasonography
to demonstrate an absence of fetal renal arteries is an al-
ternative to MRI to confirm the diagnosis if visualiza-
tion is impaired.
Although bilateral renal agenesis carries an ex-
tremely poor prognosis, in the immediate neonatal
period this is primarily attributed to pulmonary hypo-
plasia rather than renal agenesis/anuria itself. Thus,
serial amnioinfusion may present an interventional
approach to support lung development in utero. How-
ever, rigorous prospective evidence for this therapy is
lacking, and clinical trials are warranted to assess this
intervention as well as the feasibility of long-term in-
fant dialysis and ultimately kidney transplantation.
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