Congenital Anomalies of the

Urinary Tract
Dr. Noel Binayas
December 11, 2014

Audio italicized
Blue box/Red text Book notes
Embryopathies/Developmental Abnormalities are
significant in the first few years of life (pedia patients); It
has an impact in adulthood, hence, it is emphasized by
the request of the nephrologist to address the problem
of vesicoureteral reflux; It has a significant impact with
the proliferation of dialysis centers and increasing ESRD
in the adult population that requires subsequent dialysis

GU TRACT ANOMALIES
1. 10% of population
2. 30% when other anomalies are present
3. a second anomaly is common
4. part of an association of manifestations:
VATER/VACTERL - vertebral anomalies,
anorectal malformation, cardiac anomalies,
tracheoesophageal anomalies, esophageal
anomalies, renal anomalies, limb defect
(absent ulna, radius, polydactyly,
syndactyly)
5. if 1 anomaly is present, look for the
possibility that another is present

EMBRYOLOGY
Urogenital Ridge - where the genitourinary system
originates; major and only derivative of the intermediate
mesoderm
6. nephric primordium
7. gonadal primordium
8. genital duct primordium
Notochord primary organizer
Induction is from the center towards the
periphery so midline structures develop first

3 Stages of Renal Development

Stage is not a proper term since they do not follow 1
after another; However, one should be present before
another is induced to development but the structures
that arise may be dependent from prior structures in the
previous stage
Three slightly overlapping kidney systems are
formed in a cranial to caudal sequence during
intrauterine life in humans. The first of these
systems is rudimentary and nonfunctional; the
second may function for a short time during the
early fetal period; the third forms the permanent
kidney.
1. Pronephros
Primitive kidneys
functions only in the first 4 weeks and degenera
tes - nothing is derived from this stage
2. Mesonephros
replaces the pronephros at 4th week
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mesonephric tubules join the pronephric duct

to form the mesonephric or Wolffian duct

The mesonephros and mesonephric ducts are

derived from intermediate mesoderm from upper
thoracic to upper lumbar (L3) segments. They
lengthen rapidly, form an S-shaped loop, and
acquire a tuft of capillaries that will form a
glomerulus at their medial extremity. Around the
glomerulus the tubules form Bowmans capsule, and
together these structures constitute a renal
corpuscle. Laterally the tubule enters the
longitudinal collecting duct known as the
mesonephric or wolffian duct.
3. Metanephros
develops and differentiates with the inductive
influence of the cranial growth of the ureteric
bud (starts 5th week from the mesonephric
duct), which it envelopes to form the renal
cortex
This is the main anlage where your TRUE
KIDNEYS come from.
It is an entirely different structure that develops
from the ureteric bud as a result of stimulation
or inductive influence of factors present at the
tips of the ureteric bud which is derived from
around the cloaca
With the elongation and formation of the
ureteric bud and the subsequent confluence,
canalization and interconnection of the
metanephric component which develops into
the nephrons, distal collecting duct which
interconnect with the ureteric portion of the
ureteric bud
The ureteric bud defines the collecting system;
the collecting system and kidneys starts from
the distal limb of the convuluted tubules interconnections between the ureteric bud and
the metanephric tubules occur
The 2 components of the development of the
kidneys: metanephros and ureteric bud

A. Relationship of the intermediate mesoderm of

the pronephric, mesonephric,and metanephric
systems. In cervical and upper thoracic regions
intermediate mesoderm is segmented; in lower
thoracic, lumbar, and sacral regions it forms a
solid, unsegmented mass of tissue, the
nephrogenic cord. Note the longitudinal
collecting duct, formed initially by the
pronephros but later by the mesonephros.
B. Excretory tubules of the pronephric and
mesonephric systems in a 5-week-old embryo.

GENE INDUCTIONS
As the ureteric bud develops, they ascend. There are
inductors/induction that influence the surrounding
tissues of the metanephric caps which proceed to create
the developing renal tubules; Those are the so called
gene evocators or inductors

Genes involved in the differentiation of the kidney

a. WT1
Wilm's tumor gene; Wilm's tumor is
characterized
by
primitive
nephrogenic
structures - metanephric and ureteric bud
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structures; if these primitive structres remain in

the newborn/child it results to Wilm's Tumor or
Nephroblastoma
expressed by the mesenchyme
enables the tissue to respond to induction by
the ureteric bud (from the distal hindgut and
cloaca)
GDNF and HGF, also produced by the
mesenchyme, interact through their receptors RET and MET, respectively, in the ureteric bud
epithelium, to stimulate growth of the bud and
maintain the interactions. - very dynamic
exchange of signals between the ureteric buds
and the metanephric tissue
The growth factors FGF2 and BMP7 stimulate
the proliferation of the mesenchyme and
maintain (the induction of) WTI expression.

b. PAX2 and WNT4

produced by the ureteric bud, cause the
mesenchyme to epithelialize in preparation for
excretory tubule differentiation.
Laminin and type IV collagen form a basement
membrane for the epithelial cells.

METANEPHRIC SYSTEM
It gives rise to the kidney proper

Development of a metanephric excretory unit.

Arrows, the place where the excretory unit (blue)
establishes an open communication with the
collecting system (yellow), allowing flow of urine
from the glomerulus into the collecting ducts.
The collecting ducts of the permanent kidney
develop from the ureteric bud, an outgrowth of the
mesonephric duct close to its entrance to the
cloaca. The bud penetrates the metanephric tissue,
which is molded over its distal end as a cap.
Subsequently the bud dilates, forming the primitive
renal pelvis, and splits into cranial and caudal
portions, the future major calyces.
The ureteric bud gives rise to the ureter, the renal
pelvis, the major and minor calyces, and
approximately 1 million to 3 million collecting
tubules.
Each newly formed collecting tubule is covered at
its distal end by a metanephric tissue cap . Under
the inductive influence of the tubule, cells of the
tissue cap form small vesicles, the renal vesicles,
which in turn give rise to small S-shaped tubules .
Capillaries grow into the pocket at one end of the S
and differentiate into glomeruli. These tubules,
together with their glomeruli, form nephrons, or
excretory units. The proximal end of each nephron
forms Bowmans capsule, which is deeply indented
by a glomerulus . The distal end forms an open
connection with one of the collecting tubules,
establishing a passageway from Bowmans capsule
to the collecting unit. Continuous lengthening of
the excretory tubule results in formation of the
proximal convoluted tubule, loop of Henle, and
distal convoluted tubule .
9th to 12th weeks

The metanephros as it develops around the

ureteric bud - The ureteric bud arises from the
distal mesophric bud is not inducted in itself, so
it has got to be connected to the hind gut.
The metanephric tissue develops around the tip
of the ascending ureteric bud

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Metanephros ascends, rotates and

revascularizes (to assume its renal vascular
supply).
It takes out its own vascular supply, because if it
stays in this position, the kidney will be pelvic
rather than lumbar.

In the pelvis the metanephros receives its arterial

supply from a pelvic branch of the aorta. During its
ascent to the abdominal level, it is vascularized by
arteries that originate from the aorta at continuously
higher levels. The lower vessels usually degenerate,
but some may remain.

Hence, the kidney develops from two sources:

(a) metanephric mesoderm - which provides
excretory units
(b) the ureteric bud - which gives rise to the
collecting system.

EMBRYOPATHY
Developmental abnormalities from abnormal
processes of development

ASCENT OF THE KIDNEYS

The kidney, initially in the pelvic region, later shifts
to a more cranial position in the abdomen. This
ascent of the kidney is caused by diminution of body
curvature and by growth of the body in the lumbar
and sacral regions.
There is elongation of the ureterc bud, ascent of
kidneys and revascularization; The long ureter
connects to the metanephric tissue, collecting
tubes, ducts and drains into the distal
hindgut(the anterior urogenital sinus). The
cloaca divides into the anterior urogenital sinus
and the posterior rectum. The urogenital sinus
becomes the future urinary bladder.
Ectopic kidneys unascended kidneys

Failure of any of these steps to occur results in

anomalies of
9. Form - shape
10. Number
11. Position - ectopy/ wrong position
12. Volume

ABNORMALITIES IN FORM
Cystic Abnormalities
1. Autosomal recessive polycystic kidney
disease (ARPKD)
2. Austosomal dominant polycystic kidney disease
(ADPKD)
3. Multicystic dysplastic kidney (MCDK)
4. Multilocular cystic nephroma
5. Simple cysts - 1 or 2 of us will have this
***usually seen in ultrasound: multicystic/polycystic
kidneys and simple cysts (1 cm in size and usually of
no significance)

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CYSTIC DISEASE OF THE KIDNEY

GENETIC (always work up the genetic background)
Congenital Anomaly
Infantile polycystic kidneys
Adult polycystic kidneys
Juvenile nephronophthisis
Juvenile nephronophthisis-medullary
cystic disease complex (Medullary
sponge kidneys)
Medullary cystic disease
Congenital nephrosis
Familial hypoplastic glomerulocystic
kidney disease
Cysts associated with multiple
malformation syndrome

Inheritance
AR
AD
AR
-

Comparison of Autosomal Recessive and Dominant

Polycystic Kidney Disease
These are the 2 most important polycystic
kidney disease; the histologic features are done
by biopsy but can be differentiated by
cytogenetic studies

Incidence
Inheritance

Age at diagnosis 0 to late

adolescence
diagnosed earlier
but can also be
diagnosed at a
later age
Imaging
US: enlarged
US is the 1st
kidneys with
screening test
increased
which can show
echogenecity

Other organs
affected
CT is also useful
in detection

AD
AR
AD

NONGENETIC
Multicystic kidney (multicystic dysplasia)
Multilocular cyst (mulilocular cystic adenoma)
Simple cyst/ (Simple) medullary sponge kidneys
(<5% inherited)
Sporadic glomerulocystic kidney disease
Acquired renal cystic disease
Calyceal diverticulum (pyelogenic cyst)

ARPKD
1 in 6,000-40,000
Autosomal
recessive

what type of
polycystic
kidney disease
is present

ADPKD
1 in 1000
Autosomal
dominant, 100%
penetrance,
variable
expression
0-35 yrs

US: multiple,
large,
echolucent cysts
IVP: poor

Presentation

Histologic
features

IVP: poor function,

contrast streaks
extend to
cortex
CT: evaluate other
organs
Liver: Congenital
hepatic fibrosis
(with late
onset)
Vascular:
Circle of Willis
aneurysms

Younger:
renal failure
Older: liver
disease
Kidney: Collecting
duct ectasia
Liver: periportal
fibrosis

function,
distorted col.
system

Cysts: liver,
spleen, thyroid,
ovary,
endometrium,
epididymis,
seminal vesicle
If there are cysts
suspect AD
instead of AR
Renal failure

Any portion of
nephron
involved,
multiple cysts of
varying size

In congenital polycystic kidney numerous cysts form. It

may be inherited as an autosomal recessive or
autosomal dominant disorder or may be caused by
other factors.
Autosomal recessive polycystic kidney disease, which
occurs in 1/5,000 births, is a progressive disorder in
which cysts form from collecting ducts. The kidneys
become very large, and renal failure occurs in infancy
or childhood.
Autosomal dominant polycystic kidney disease, cysts
form from all segments of the nephron and usually do
not cause renal failure until adulthood. The autosomal
dominant disease is more common (1/500 to 1/1,000
births) but less progressive than the autosomal
recessive disease.

ABNORMALITIES IN NUMBER
A. Renal Agenesis - less than normal in number
13. Unilateral usually associated with vascular
accidents during the development of the kidneys
or failure of one anlage to develop.
14. Bilateral
ex. A baby with bilateral renal agenesis
presents with dyspnea, tachypnea; Carried
by an oligyhydramniotic pregnancy and
delivered CS; Xray showed compressed
Page 5 of 10

thoracic structures and chest unexpanded.

There are excessive creases in the feet and
cheeks. Dx: Potter Syndrome - incompatible
with life; sustained by neonatal dialysis
while waiting for renal transplant so that it
can survive
Congenital hydronephrosis in infant - US:
hydrnephrotic kidney in 1 side usually
caused by uretero-pelvic obstruction,
congenital stenosis
1 absent kidney in a child is undetectable
since the other compensates
OLIGOHYDRAMNIOS develops due to anuria.
Because of the low volume of amniotic fluid
the fetus is all cramped up inside the uterus
and the muscles become atonic. Atonic
muscles causes deep creases to develop in
the skin such as the deep transverse creases
on the face which is a characteristic finding
of the syndrome. The lungs are also unable
to expand becoming hypoplastic at birth.

Genital
(Female)

-unicornuate or
didelphic uterus
-duplicate or
absent vagina

Pulmonary
CV
GI
Esophageal
Orthopedic

Others

-septal, valvular
defects
-imperforate
anus
-stricture, atresia
-vertebral,
phalangeal
anomalies
Syndromes
-VATER, Poland,
Turners

-rudimentary,
anomalous or
absent uterus,
vagina
-hypoplastic or
absent ovaries
-pulmonary
hypoplasia
-present
- imperforate
anus
-club feet
-spina bifida
-characteristic
(Potter) facies

ABNORMALITIES IN POSITION
Potter sequence, characterized by anuria,
oligohydramnios (decreased volume of amniotic
fluid) and hypoplastic lungs secondary to the
oligohydramnios.
B. Supernumerary Kidneys
Caveat: hydronephrosis sec to obstruction of
ureteropelvic junction at the outlet of the
calyxes, a congenital stricture is present - a
common cause
Common Associations with Renal Agenesis
The kidneys are mesodermal in origin, hence, it
is associated with other mesodermal problems
which is distributed in general areas of the body

Urologic

Genital( Male)

Unilateral
-urethral
absence or
atresia
-asymmetric or
hemitrigone
-contralateral
renal ectopia
-absent vas
deferens,
seminal vesicle

Bilateral
-ureteral atresia
-absence or
hypoplastic
bladder
-malrotation

Ectopia and Fusion Anomalies

1. Simple renal ectopia - lower than usual position
2. Crossed renal ectopia - Right kidney drained by
left draining ureter - right renal ectopia, left
kidney drained by right draining ureter- left
renal ectopi.
3. Horseshoe kidney

-hypospadias
-penile agenesis
-undescended
testis
Page 6 of 10

 General rule: when you have an abnormal

kidney, look for associated abnormalityVATER/VACTERL

URETER DUPLEX SYSTEM

The kidneys are pushed so close together during

their passage through the arterial fork that the
lower poles fuse. The horseshoe kidney is usually at
the level of the lower lumbar vertebrae, since its
ascent is prevented by the root of the inferior
mesenteric artery. The ureters arise from the
anterior surface of the kidney and pass ventral to
the isthmus in a caudal direction. Horseshoe kidney
is found in 1/600 people.

complete or partial
usually associated with an ectopic opening in the
bladder
usually the abnormal one is the superior ureter in
the duplex system; the superior pole becomes
hydronephrotic
the ureter drains in the bladder or in the vagina or
vestibule -usually in females

Common Associations with Ectopic Kidney

1st thing to ask yourself - what other
abnormalities are present
A. Musculoskeletal
Vertebral (as in VATER), rib anomalies
Cranial Asymmetry
Absent bones - absent ulna, missing cervical
spine, extra ribs
B. Urologic
Vesicoureteral reflux - common
UPJ obstruction
Contralateral agenesis
C. Genital
Male patients:
Undescended testis
Hypospadias
Urethral duplication
Female patients:
Uterine or vaginal anomalies, atresia,
agenesis
D. Others
Cardiovascular
Gastrointestinal

Duplication of the ureter results from early splitting of

the ureteric bud. Splitting may be partial or complete,
and metanephric tissue maybe divided into two parts,
each with its own renal pelvis and ureter. More frequ
ently, however, the two parts have a number of lobes
in common as a result of intermingling of collecting tu
bules. In rare cases one ureter opens into thebladder,
and the other is ectopic, entering the vagina, urethra,
or vestibule. This abnormality results from developme
nt of two ureteric buds.One of the buds usually has a
normal position, while the abnormal bud moves down
together with the mesonephric duct. Thus it has a low
, abnormal entrance in the bladder, urethra, vagina, o
r epididymal region.
URETERAL OBSTRUCTIONS AND MALFORMATIONS
1. Ureteropelvic junction obstruction in children (UPJ)
- most common cause of hydrnephrosis; in infancy

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2.
3.
4.
5.

6.
7.

there is dilated calyxeal system and enlarged

kidneys
Ureteral duplication
Triplication, Quadriplication
Retrocaval Ureter - the ureter passes behind the
vena cava
Megaureter associated with a megabladder and
megacolon (hirschsprung disease); Megacystic
hypoganglionic syndrome can be seen also in Eagle
Barrett syndrome/prune belly syndrome obstruction of the bladder neck enlarges the
abdomen in the intrauterine life (pot belly fetus)
and form the prune belly of the newborn because
of the extra folds in the abdomen because of the
deficiency of abdominal wall
Ectopic Ureter
Ureterocoeles
Prune belly syndrome or abdominal muscle wall
agenesis occurs due to the failure of the lateral
mesoderm to develop.
It is usually associated with megacystis and
hydronephrosis.
Babies with PBS are prone to respiratory
infections since the abdomen cannot participate
in respiration and the diaphragm is lax. They
could not expectorate phlegm. It is usually the
cause of death for these children.
Uropathies Detectable by Prenatal Sonography
US - very good in screening; useful in detecting
urogenital abnormalities)
Do not simmply request for hepatobiliary or
renal ultrasound, request for ultrasound of the
whole abdomen to eval other organs most
important abdominal studies in detecting
congenital anomalies even in the neonatal
period
Condition

Frequency

Ureteropelvic junction obstruction

Multicystic dysplastic kidney

1: 2,000
1: 3,000

Primary ureterovesical junction

obstruction
Ectopic Uterocoele or ureter

1: 10,000

Posterior urethral valves - in boys

1: 8,000

Prune belly syndrome (rarest)

1: 40,000

Vesicoureteral reflux

1: 100

VESICOURETERAL REFLUX (VUR)

1: 10,000

denotes the retrograde flow of urine from the

urinary bladder to the upper urinary tract
Primary VUR (true congenital) vs Secondary VUR
(associated with adult HPN or permanent renl injury
that starts during infancy)

Primary VUR
Congenital anomaly of the
UVJ - more common

Secondary VUR
Altered physiology in:
increased intravesical
pressure
obstructed, poorly
compliant bladders
lower tract anomalies:
4. ureteral ectopia
5. ureterocoeles
6. bladder extrophy
7. prune belly
syndrome
diagnosed by imaging,
voiding cystourethrogram

VUR = Reflux Nephropathy

Renal damage secondary to chronic pyelonephritis kidneys are destroyed; seen in adults but may be
properly dealt with during childhood
VUR increases the morbidity of UTI (pyelonephritis)
by involving the upper urinary tract
Renal scarring is the most important pathology in
renal infections that can lead to VUR
VUR Incidence and Morbidity
97% of children with renal scarring showed VUR.
Renal failure is the most ominous sequelae of VUR.
threefold increase in risk of hypertension
reduced somatic growth in childhood
pregnancy complications in adulthood
VUR is the most significant factor you want to
eliminate if you want to decrease the incidence of
adult renal disease
Childhood UTI and VUR
40% are found to have VUR
inverse correlation with age
average age of diagnosis: 2-3 years upon work-up
following a febrile UTI - sometimes there is a low
rate of diagnosing UTI in children; achild not
growing properly may have recurring UTI
75% - 80% discovered to have primary VUR are girls.
Males predominate in newborn worked-up for VUR.
increased prevalence among siblings of children
with VUR
Page 8 of 10

more common in fair-skinned children of Northern

European descent - recently the incidence is already
the same, they just had better means of diagnosing
and awareness

VOIDING CYSTOURETHROGRAM (VCUG)

- a means to diagnose VUR

iodinated contrast instillation, or
radionuclide cystography
Indications:
an evaluation following UTI in children
postnatal evaluation of newborns with
prenatally diagnosed hydronephrosis
high risk children:
o with renal anomalies
o lower tract anomalies
o siblings with history of VUR
International Reflux Study Classification, 1992
- depends on how much reflux occurs
Grade
Grade I
Grade II
Grade III

Grade IV

Grade V

Characteristics
Reflux into the ureter only
Reflux into the ureter, renal pelvis and
calyxes
Mild or moderate dilation of the ureter
and renal pelvis with no or minimal
forniceal blunting
Moderate dilation and tortuosity of the
ureter with blunting of the fornices but
maintenance of the papillary impressions
Gross dilation and tortuosity of the ureters
and pelvis with absence of papillary
impressions
smoothens out the calyxes

Blood pressure - as early as possible to detect

HPN

Surgery
Goal of surgery is to create an adequate
intravesical segment of the ureter to prevent reflux.
(change the angulation or ball valve mechanism)
Intravesical or extravesical route
90-100% success rates
STING (endoscopic subureteric injection
technique) using a bulking agent (PTFE, Teflon,
etc.)
close the ureter and transplant to another area in
the bladder

BLADDER AND URETHRA

During the fourth to seventh weeks of development
the cloaca divides into the urogenital sinus anteriorly
and the anal canal posteriorly
Bladder is derived from the hindgut and
urogenital sinus

Hydronephrosis is a late manifestation of

obstruction
Prognosis and treatment
Most cases of primary VUR ()some weakness in the
junction) in children will resolve spontaneously.
Expectant Management
Sterilize urine until reflux is resolved
(Nitrofurantoin, Cotrimoxazole) - more common
in our setting in adults
Monitoring of UTI episodes (fever, urine
cultures), reflux (VCUG) and kidneys (scans) - all
should undergo VCUG but it is time consuming
Growth profile

Page 9 of 10

 These surgeries, especially in children, disrupt

their psychosexual development. As physicians,
you should also become sensitive to these
issues.
Notetakers: C1, C2, rV, pyolo
Editor: C1
Sources: Slides, Lecture Audio, Jax Notes, Langmans Embryology

Divisions of the cloaca into the urogenital sinus and

anorectal canal. The mesonephric duct is gradually
absorbed into the wall of the urogenital sinus, and
the ureters enter separately. A. At the end of the
fifth week. B. 7 weeks. C. 8 weeks.

Urethral valves - in boys, the posterior urethral

valves creates a ball valve mechanism; shaft of the
urethra - anterior portion is mobile
Bladder exstrophy
Bladder exstrophy is a ventral body wall defect in
which the bladder mucosa is exposed.
o Epispadias is a constant feature, and the open
urinary tract extends along the dorsal aspect of
the penis through the bladder to the umbilicus.
o Exstrophy of the bladder may be caused by a lack
of mesodermal migration into the region
between the umbilicus and genital tubercle,
followed by rupture of the thin layer of
ectoderm. This anomaly is rare, occurring in
2/100,000 live births.

Epispadias
Hypospadias - Failure of fusion of the urethral folds
If you want to evaluate the bladder or ureter or
kidney, scan the whole abdomen
The important thing to remember in the surgical
correction of any congenital anomaly whatever this
may be The first surgery must be right! Subsequent
operations must advance Or else be definitive.
Increase in suicide rates in patients with
congenital anomalies of the external genitalia
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