1. Prenatal diagnosis of congenital uropathies
Elena Levtchenko
Leuven, Belgium
Moscow, October 22, 2013

2. Gifted by R. Kleta
?
Pediatric
Pediatric consult consult
birth

3. Definition of congenital uropaties
(CAKUT)
• CAKUT: congenital anomalies of kidney
and urinary tract
– 20-30% of all anomalies identified in
prenatal period (Queisser et al. 2002)
– Overall rate: 0.3-1.6 per 1000 newborns
(life and stillborn) (Wissel et al. 2005, Caiulo et al. 2012)
– 30-60% of pediatric and young adult
patients with ESRD (Harambat et al. 2012, Wuhl et al. 2013)

4. Development of human pronephros
Song et al. Pediatr Nephrol
2011

5. Prenatal kidney/urinary tract imaging
• Urinary bladder and kidneys can be visualized
by ultrasound (US) starting from the 12th week
gestational age (GA)
• Cortico-medullary differentiation - starting from
18-20 weeks GA
• Screening US for congenital malformations
(including CAKUT) at 2nd trimester of pregnancy
(18-22 weeks GA)
1st prenatal consult

7. Information from gynecologist
• Inter-polar kidney diameter (in SD for GA) for both
kidneys
• Position of the kidneys
• Cortico-medullary differentiation, aspect renal
parenchyma
• Dilatation of collecting system?
• renal pelvis (AP diameter or grade of hydronephrosis)
• ureters
• Presence/dilatation of urinary bladder
• Amniotic fluid (eyeballing, AF index or deepest pool)

8. Aim of prenatal consult
• Diagnosis of CAKUT
– Isolated (unilateral vs bilateral/syndromal)
• Prediction of prognosis
– Pregnancy:
• Termination of pregnancy (TOP):
– 4% in isolated CAKUT, 50% in syndromal cases (Wissel et al. 2005)
• Indications for fetal surgery
• Indications for delivery:
– Induction/Delivery in tertiary centrum?
– Child
• Survival/Renal outcome
• Postnatal treatment

9. Prenatal  postnatal CAKUT diagnosis
EUROSCAN study: Fetal US of 709,030 birth in 12 European
Countries
Wiesel et al. EJMG 2005

10. Gynecological classification of antenatal
hydronephrosis
• Antenatal hydronephrosis: incidence 1-5% in general fetal population
• Classification of Society of Fetal Urology

11. “Pediatric classification” of antenatal
hydronephrosis
Bladder filling
?
Grade 1-2
Grade 2-3
Grade 4

12. Prognosis of antenatal hydronephrosis
Lee et al. Pediatrics 2006. Meta-analysis of 1,645 studies -> 17 studies sufficient
quality

13. Termination of pregnancy
N=50 (2008-2013)
Hyndrickx & De Catte, IPNA 2013

14. Case (prenatal follow-up)
•
•
•
Gravida 3, Para 2
Two healthy children
25 weeks gestational age (GA):
– Male, severe oligohydramnios
– Talipes equinovarus left
– Bilateral hydroureteronephrosis grade 4
– Megacystis
– Dilatation of the proximal urethra
 LUTO (posterior urethral valves)
• TOP?
• Fetal surgery?
• 25 weeks GA: placement of vesico-amniotic
shunt
 increase of amniotic fluid

15. Case (postnatal follow-up)
• Birth weight 2.4 kg, Apgar 8/9
• Postnatal period:
– Pneumothorax, mild lung dysplasia
– Urethra valves, no VUR
– Renal function at 1 week:
•
creatinine: 2.3 mg/dl
• Treatment:
–
–
–
–
Urethral valve resection
Intermittent catheterisasion
Intravesical oxybutinin, AB prophylaxis
Supportive treatment of CKD

16. Glomerular filtration rate at 2 years?
• < 15 ml/min/1,73 m2
• 15-30 ml/min/1,73 m2
• 30-60 ml/min/1,73 m2
• 60-90 ml/min/1,73 m2

17. Morris et al. Prenatal diagnosis 2007:
Mate-analysis of biochemical and US parameters to predict
postnatal renal function in congenital lower urinary tract obstruction
Best predictive value: renal cortical appearance, sensitivity 81% and specificity 59%

18. Klein et al. Sci Transl Med 2013: proteomics study of fetal urine to
predict postnatal renal function in congenital lower urinary tract
obstruction

19. Klein et al. Sci Transl Med 2013

20. Indications for fetal surgery
Only in Low-Urinary Tract
obstruction (LUTO)
Morris et al. Lancet 2013:
Results of PLUTO trial:
N=31 pregnancies with PUV,
16 – vesicoamniotic shunt (VAS)
15 – concervative treatment (CT)
•
•
•
•
•
VAS:
1 intrauterine death
3 TOP
4 death <28
days
8 survived
2 normal RF
•
•
•
•
•
CT:
1 intrauterine death
2 TOP
8 death <28
days
4 survived
0 normal RF

21. Indications for delivery induction
• Efforts to continue pregnancy to prevent
complications of premature birth:
– 34-36 weeks in case of severe
oligohydramnios?
• Indications for delivery in tertiary center:
• Anticipated requirement of renal replacement
therapy
• Anticipated requirement of complex surgery in
neonatal period
• Anticipated requirement in tertiary neonatal care

22. Can standard prenatal examinations
predict postnatal outcome of renal
function?
An Hindryckx
Luc De Catte
Prenatal imaging studies
Anke Raaijmakers
Postnatal follow-up

23. Standard examinations
• 2D fetal ultrasound:
– Kidney length
– Pyelum (grade hydronephrosis,
anterio-posterior diameter)
ureter width
– Bladder diameter, aspect
• Amniotic fluid examination
• Fetal serum (2-MG, cystatin C,
caryotype, urine (electrolytes,
osmol)
Advanced examinations
• 3D fetal ultrasound
• Fetal urine production
• Fetal cortex blood flow
• Fetal MRI
• Proteomics and metabolomic
studies of amniotic fluid

24. 3D renal ultrasound
Kidney/pyelum volume measurement:
by Virtual Organ Computer-aided AnaLys
(VOCAL) with sono-AVC (automated volume
count) for fluid/filled spaces segmentation

25. 3D renal ultrasound
Potential:
•
Volume is better reflecting
function compared to renal
pelvic diameter (Nam et al. 2012)
•
Distinction between pyelum and
renal parenchyma  cortex
volume
Limitations:
Inversion rendering
• Lack of standardization:
• Methodology (imaging planes,
anatomical landmarks,
repeatability)
• Lack of validated normal
values
• Data analysis and storage
(depending on producent)

26. Reference curve for 3D renal volume
ml
Hindryckx et al. 2013, IPNA Poster P-SUN009

27. Fetal urine production
Potential:
• (Decreased) fetal
diuresis might predict
kidney function
Sono-AVC combined with VOCAL-technique
• Limitations:
• Lack of validated
normal values
• High variation

28. Fetal kidney perfusion
• Peak systolic velocity (PSV)
• Flow velocity integral in renal vein correlated to
kidney cortex volume (FVI x HR/renal cortex
volume)

29. Normal fetal kidney perfusion
cm/se
c
Hindryckx et al. 2013, IPNA Poster P-SUN009

30. Conclusions
• Interaction between gynecologist and
pediatrician for prenatal diagnosis of
CAKUT
• Prenatal consult aimes to make diagnosis,
define severity and prognosis, pre- and
postnatal follow-up; objective information
for the parents
• Good prognostic markers for renal function
outcome are limited and are a subject of
intensive research

31. Pediatricians/pediatric
nephrologists should be involved
in prenatal follow-up of patients
with CAKUT!

32. Acknowledgments
Katholieke Universiteit Leuven
An Hindryckx
Luc De Catte
Anke Raaijmakers
Djalila Mekahli
Karel Allegaert
Inserm Toulouse
Joost Schanstra
Stéphane Decramer
Jean-Loup Bascands
UCL University College London
Paul Winyard
Universitätsklinikum Heidelberg
Franz Schaefer
Elke Wühl
Anke Doyon

33. THANK
YOU!
Fons Sapientiae by Jef Claerhout
Leuven, Belgium

34. Embriology of kidney development

35. Abnormal kidney development
Song et al. Pediatr Nephrol
2011

36. Molecular regulation of kidney development (1)
M. Little et al. Current Topics in Developmental Biology
2010

37. Molecular regulation of kidney development (2)
TownesBrocks
syndrome
DenisDrash
syndrome
Brachiootorenal
syndrome
Oculorenaal
syndrome
M. Little et al. Current Topics in Developmental Biology
2010

38. Role of HNF1 beta in kidney development
Renal
cysts –
diabetes
syndrome
Naylor et al. JASN 2013

39. Case 1 (prenanal follow-up)
• Gravida 2, Para 0
• In vitro fertilization
• 24 weeks gestational age (GA):
– Male foetus
– Oligohydramnios
– Bilateral hydroureteronephrosis grade 4
– Megacystis
– Dilatation of the proximal urethra
 LUTO (posterior urethral valves)
• Weekly follow-up
• 26 weeks GA: foetal serum 2-MG: 5.9
mg/L (ref <4.9
• Induction of delivery at 34 weeks due to
severe oligohydramnios

40. Case 1 (postnatal follow-up)
• Birth weight 2.3 kg, Apgar 8/8
• Postnatal examinations:
– Prenatal diagnosis is confirmed, VUR 5 Le
– Polyuria after placement of bladder catheter
– Renal function at 1 week:
•
creatinine: 2.3 mg/dl
• Treatment:
–
–
–
–
Urethral valve resection
Intravesical oxybutinin, AB prophylaxis
Ureter re-implantation at 1.5 years
Supportive treatment of CKD
 GFR at 2 years (Cr-EDTA clearance): 59 ml/min/1.73 m2

41. Morris et al. BJOG 2009. Meta-analysis : antenatal ultrasound to predict
postnatal renal function in congenital lower urinary tract obstruction
(13 studies, 215 women)
Best predictive value: renal cortical appearance, sensitivity 0.57 (95% CI 0.370.76) and specificity 0.84 (95% CI 0.71-0.94)

42. AF 4-quadrant index