1. No category

Urinary tract
anomalies
of the fetus
Embryology
TRONDHEIM
Harm-Gerd K Blaas
National Center
for Fetal Medicine
Dept Ob & Gyn
Skien, juni 2015
Trondheim - Norway
Intermediate mesoderm
Stage 7, week 4+1-2 (LMP)
Gastrulation
Epithelium cell –
bottle cell –
mesenchymal cell
– mesodermal cell
Epiblast cells migrate
distance of ≈ 1 µm
(primitive streak è
mesoderm),
speed 0.04 µm/hr
Intermediate mesoderm
(arrows)
Stages 9, 10 and 12
Folding process during week 5 (LMP)
* Future bowel
*
Me
Ectod
so
erm
de
rm
Endoderm
Me
so
de
rm
Pronephric and mesonephric
(Wolffian) duct
Intermediate mesoderm
Cranial
neural
pore
Urogenital system
Heart
Intermediate mesoderm
£  Nephrogenic
cord
Pronephros
n  Mesonephros
n  Metanephros
Yolk sac
Ureteric bud &
metanephric
blastema è
reciprocal
inductive effects
Mesonephric
duct
n 
l 
l 
l 
Cord
Duct (pronephric, mesonephric)
Tubules
Glomerular capsule
Glomerulus
£  Gonadal
ridge (+ coelomic epithelium and
primordial germ cells)
l 
Indifferent gonad
Duct (mesonephric, paranephric)
Ureteric
bud
Me
l 
Stages 10-11
so
ne
du phri
ct
c
l 
Ureteric buds continue to
bifurcate until ≈ 32nd week
(1-3 000 000 collecting ducts)
Origin of metanephric kidneys
A. metanephric blastema origins from intermediate mesoderm
B. ureteric buds grow into metanephric blastema
C. bifurcation; superior and inferior lobes
D. Additional lobes form during next 10 weeks
Development of renal collecting
system and nephrons
Metanephric Nephric
tissue cap
vesicle
Glomerulus
+
Bowman’s
capsule
Proximal & distal
convoluted tubes
and
Henle’s loop
Embryonic kidney
9 weeks LMP based
Future
urinary
bladder
Early fetal kidney
Rutineultralydundersøkelse
u 
Ultralydundersøkelse
tilbys i ca 17. til
19. svangerskapsuke
u 
u 
u 
u 
10 weeks CRL 38 mm
Terminbestemmelse (biometri)
Antall fostre
Morkakens plassering
Fosterets anatomi og utvikling
11 weeks LMP based
Rutineultralydundersøkelse
ca 17. til 19. svangerskapsuke
Fosterets anatomi & utvikling
u 
u 
u 
u 
u 
u 
u 
u 
u 
u 
u 
Kranium
Hjerne-, ventrikler
Ryggsøyle
Halsregion
Hjerte
Mage-, tarmsystem
Nyrer
Urinblære
Kropp
Ekstremiteter
Fostervann
Fetal urinary tract anomalies
Studies
Congenital urinary tract
anomalies
u 
u 
u 
Fetal renal tract anomalies in a
selected fetal population è outcome
One of the most commonly
identified anomalies at prenatal
ultrasound
Incidence: 1 : 250 – 1000
Majority due to obstruction
u 
u 
u 
Ureteropelvic junction
Ureterovesical junction
Level of bladder neck
Merril et al 1997
Tertiary referral center, Utrecht
Structural
anomalies
n=151
37.6%
Death related to renal tract anomalies
n=84/151
55.6%
Urinary
tract
dilatations
n=247
61.4%
Miscellaneous
n=4
0.9%
Death, total
n
Structural disorders 87/121
Obstructive disorders 33/121
Miscellaneous
1/121
Total
121
%
72
27
0
100
n=22/247
8.9%
N=402
2005 UOG
Damen-Elias
N=402
30%
Fetal renal tract anomalies
in an autopsy population
Trondheim
Conditions with dilatation/
obstruction of urinary tract
= 20.9%
Wiesel A, Queisser-Luft A, Clementi M, et al. Prenatal detection of congenital renal malformations by fetal
ultrasonographic examination: an analysis of 709,030 births in 12 European countries. Eur J Med Genet 2005; 48:131
Non-selected population Trondheim
area,
N ≈ 200 000, 2 700 births
Dilatation of upper tract detected 259 (28%), total 309 (27%)
One scanning unit
Lower tract obstruction detected 19 (2%), total 29 (2.5%)
One delivery
department
One pediatric /
neonatal
department
Wiesel A, Queisser-Luft A, Clementi M, et al. Prenatal detection of congenital renal malformations by fetal
ultrasonographic examination: an analysis of 709,030 births in 12 European countries. Eur J Med Genet 2005; 48:131
Fetal ultrasound 1990 – 2012
Non-selected population
N = 60 650
Urinary tract anomalies
Non-selected population
tilsvarer 1 årskull fødsler i Norge
prenatally
detected
u 
All anomalies
u 
Urinary tract anomalies
%
Cystic lesions 66 / 265 (25%)
prenatally not
detected
1047 1.73
?
252 0.42
13 *
Simple cysts
u  Isolated
u  Associated
anomalies
u  Chromosomal aberration
N = 66
% = 100
* registered within few weeks postnatally:
Multicystic/dysplastic
APKD
Unilateral Bilateral Dysgenesis
2
–
1
39
7
4
5
2
–
6
–
–
3
4
50
76
7
11
6
9
10 hydronephroses/dilated ureter, 1 PUV, 1 simple renal cyst,
1 bilateral renal agenesis
Urinary tract anomalies
Non-selected population
Urinary tract anomalies
Non-selected population
Hypoplasia, agenesis, ectopia,
duplications, a.o. 63 / 265 (24%)
Dilatations / obstructions 136 / 265 (51%)
Hypoplastic/absent Ectopic, pelvic, double Horseshoe a.o.
Unilateral Bilateral
u  Isolated
u  Ass.
anom.
u  Chrom. aberration
N = 63
% = 100
Unilateral Bilateral
13
14
1
5
–
–
12
2
–
1
–
–
1
2
12
28
44
5
8
14
22
1
2
15
24
Hydronephrosis
/dilated ureter
Unilateral Bilateral
u  Isolated
63
37
u  Associated anomalies
16
2
u  Chromosomal aberration
3
1
N = 136
% = 100
82
60
40
30
Urinary tract anomalies
Non-selected population
n
%
Cystic /multicystic dysplastic / 66 25
polycystic lesions etc
u  Hypoplasia, agenesis, ectopia,
63 24
duplications etc
u  Dilatations / obstructions
136 51
u  Total
265 100
u 
Obstructive uropathy or
urinary tract dilatation
PUV/urethral
obstruction
12
2
14
10
Obstruction
of the urinary tract
1
Pyelectasis
Measurement of
renal pelvis
Longitudinal plane
Horizontal plane
1  Uretero-pelvic junction
2  Uretero-vesical junction
2
3  PUV
Lower u
rina
3
ry tract
obstruc
tion
LUTO
4  Urethral stenosis, atresia
4
Renal pelvis AP diameter
N=663
10 mm
Mild pyelectasis
5 mm
th
90
e
perc
When assessing the variability in individual kidneys over time, we
found the mean variation (minimum to maximum) for the sum of the
AP and transverse measurement to be 7.61 (SE 4.26) mm and for
the AP measurement alone to be 3.80 (SE 2.49) mm
ntile
Causes of antenatal hydronephrosis
u  Anomalous
UPJ or UPJO
kidney
u  Retrocaval ureter
u  Primary obstructive
megaureter
u  Non-refluxing non-obstructed
megaureter
u  Vesicoureteral reflux
u  Midureteral stricture
u  Multicystic
u  Ectopic
ureterocele
ureter
u  Posterior urethral valves
u  Prune belly syndrome
u  Urethral atresia
u  MMIHS
u  Hydrocolpos
u  Pelvic tumor
u  Cloacal abnormality
Vesico-ureteric reflux
u  Ectopic
MMIHS, megacystis–microcolon–intestinal hypoperistalsis syndrome; UPJ,
ureteropelvic junction; UPJO, ureteropelvic junction obstruction
from the book: Nephrology and Fluid/Electrolyte Physiology: Neonatology Questions and Controversies
William Oh, Jean-Pierre Guignard, Stephen Baumgart.
2008, Chapter 19, R Chevalier
Vesico-ureteric reflux (VUR) is
responsible for 10–40% of
antenatally detected
hydronephroses and is bilateral
in almost half of the cases
Herndon, et al., J Urol, 1999
Nguyen, et al., J Ped Urol, 2010 and 2014
Av 142986 levende fødte hadde 389
(2,7 per 1000) misdannelser i nyrer/
urinveier. Prevalensen var
høyere for barn født 1997–2006 (241/70
217; 3,4 per 1 000) enn 1987–96 (148/72
769; 2,0 per 1 000) (p < 0,001).
Andelen barn med prenatalt påviste
anomalier økte signifikant fra første
tiårskohort (35/148; 24 %) til siste
(125/241; 52 %) (p < 0,001). Økningen
skyldtes flere prenatalt diagnostiserte
tilfeller av hydronefrose, henholdsvis
27 (0,4 per 1 000) og 96 (1,4 per 1000) i
de to tiårskohortene (p < 0,001)
Hans Randby,
Alf Meberg,
Hussain A.G. Yassin,
Line Merete Tveit,
Sara Viksmoen Watle,
Ole Jørgen Moe
2009 Tidsskriftet
Hydronephrosis –
false positive?
Dilemma:
1. Fosterpopulasjon ≠ pediatrisk populasjon
2. Funn av urinveispatologi hos et foster er
indikasjon for videre diagnostikk
3. Hvor setter vi cut-off point for AP-diameter?
Classification of
hydronephrosis
Measurement in 2nd trimester
Hydronephrosis (18-23 weeks)
268/11465 (2.3%)
Mild
4 – 6 mm
Moderate/severe
≥ 7 mm
Persistent hydronephrosis if ≥ 10 mm
in third trimester
None of fetuses with mild
hydronephrosis and ≈ 1/3 fetuses
with persistent moderate/severe
hydronephrosis required postnatal
surgery
Antenatal hydronephrosis as
a predictor of posytnatal
outcome: A meta-analysis
Richard Lee et.al., 2006
Mild
AP-diameter,
mm
AP-diameter,
mm
2nd trimester
3rd trimester
≤7
≤9
Moderate
7–10
9–15
Severe
≥ 10
≥ 15
2010
Measurement of renal pelvis in 2nd and 3rd trimester
2014
2nd trimester at
≈ 18-20 weeks
Mild
5–7–9
Significant
≥ 10
> 20
mm
mm*
mm èsurgery
≤ 7
≥ 9
≥ 10
mm = normal
mm
further
mm follow up
Follow up
at 32 weeks
≥ 10 mm: 1/3 need post natal surgery, Sairam et al: UOG 17:191, 2001
*frequently associated with uropathy (e.g. reflux)
Uretero-pelvic junction obstruction
1
Obstruction
of the urinary tract
1  Uretero-pelvic junction
2
2  Uretero-vesical junction
3  PUV
Lower u
rina
3
4
3rd trimester
LUTO
Lower urinary tract obstruction
/ 10 000 births
4  Urethral obstruction, atresia
LUTO
Posterior urethral valve
syndrome (PUV)
Urethral atresia
Urethral stenosis/obstruction
v
Antenatal detection of LUTO
gives the option of assessment
and potential for in-utero
treatment
Robyr et al 2005
Morris & Kilby 2011
ry tract
obstruc
tion
LUTO
LUTO
Large urinary bladder
Bilateral renal/ureteral changes due to obstruction
u  Oligo- or anhydramnion
u 
u 
Fetal treatment?
Aim of fetal therapy
u Prevention
of pulmonary hypoplasia
u Preservation of renal and bladder function
Prognostic criteria
1.
Urine biochemistry at 20 weeks gestation
Creatinine
Na +
Cl Osmolality
ß2-microglobulin
< 150 mmol/l
< 100 mmol/l
< 90 mmol/l
< 210 mOsm
<
5 mg/L
High levels of ß2-microproteins in the urine indicate
defect of renal tubular reabsorption
2.
Fetal obstructive uropathy
Sonography no cortical cysts, and normal
echogenicity of cortex
Double kidneys/ureteres
• 
Incidence 1:1000
u  Unilateral or bilateral
u  Hydronephrosis, -ureter
u  Multicystic-dysplastic kidney
u  Ureterocele (cyst in the bladder)
Grav 1 Para 0
23 years
LMP 301099, EDD 240800
23 weeks: pyelectasis
25 weeks: normal
30 weeks:
Anhydramnios
Hydronephrosis
Large urinary
bladder
Scan of fetal urinary
tract
Consider
Amniotic fluid amount
Two kidneys and renal pelves
Adrenal glands
Ureteres usually not visible
One urinary bladder
Gender
Fetal urinary tract anomalies
Consider
u False negative (Approximately 40% of children
requiring surgery for renal tract pathology will have a
normal antenatal ultrasound examination - Bhide et al 2005;
UOG)
u False
positive findings
Re-evaluate renal pelvis dilatation ≥ 7-10 mm at
mid-trimester routine scan
Re-evaluate postnatally cases with renal pelvis
dilatation ≥ 9 mm at 32 weeks re-scan
Incision of ureterocele
At 30 weeks puncture and
incision of ureterocele
Delivery at 34 weeks
3330 g, APGAR 9-10
Later reimplantation of ureter
Fetal urinary tract anomalies
Consider
The prognosis of isolated unilateral
defects is very good, therefore, if you
detect an urogenital anomaly, find
out:
Are there associated anomalies?
What is the karyotype?
Which gender?
Counseling the parents
Tertiary center
Surveillance
Specialized neonatal unit
Pediatric surgeon
Time and place of delivery