Download - 2-2. CAKUT. Elena Levtchenko (eng)
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Prenatal diagnosis of congenital uropathies
Elena LevtchenkoLeuven, Belgium
Moscow, October 22, 2013
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Pediatric consult
birth
?
Gifted by R. Kleta
Pediatric consult
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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)
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Song et al. Pediatr Nephrol 2011
Development of human pronephros
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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
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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)
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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
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Prenatal postnatal CAKUT diagnosis
EUROSCAN study: Fetal US of 709,030 birth in 12 European Countries
Wiesel et al. EJMG 2005
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Gynecological classification of antenatal hydronephrosis
• Antenatal hydronephrosis: incidence 1-5% in general fetal population
• Classification of Society of Fetal Urology
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“Pediatric classification” of antenatal hydronephrosis
Grade 4
Grade 1-2Grade 2-3
Bladder filling ?
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Lee et al. Pediatrics 2006. Meta-analysis of 1,645 studies -> 17 studies sufficient quality
Prognosis of antenatal hydronephrosis
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Termination of pregnancy
Hyndrickx & De Catte, IPNA 2013
N=50 (2008-2013)
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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)
• 25 weeks GA: placement of vesico-amniotic shunt increase of amniotic fluid
• Spontaneous partus at 33 weeks GA
• TOP?• Fetal
surgery?
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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
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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
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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%
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Klein et al. Sci Transl Med 2013: proteomics study of fetal urine to predict postnatal renal function in congenital lower urinary tract
obstruction
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Klein et al. Sci Transl Med 2013
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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 intra-
uterine death
• 3 TOP• 4 death
<28 days• 8 survived• 2 normal
RF
CT: • 1 intra-
uterine death
• 2 TOP• 8 death
<28 days• 4 survived• 0 normal
RF
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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
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Can standard prenatal examinations predict postnatal outcome of renal
function?
An Hindryckx
Luc De Catte Anke Raaijmakers
Prenatal imaging studies Postnatal follow-up
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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
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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
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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 volumeLimitations:
• Lack of standardization:• Methodology (imaging
planes, anatomical landmarks, repeatability)
• Lack of validated normal values
• Data analysis and storage (depending on producent)Inversion rendering
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Reference curve for 3D renal volume
Hindryckx et al. 2013, IPNA Poster P-SUN009
ml
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Fetal urine production
Sono-AVC combined with VOCAL-technique
Potential:• (Decreased) fetal
diuresis might predict kidney function
• Limitations:• Lack of
validated normal values
• High variation
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Fetal kidney perfusion
• Peak systolic velocity (PSV)• Flow velocity integral in renal vein
correlated to kidney cortex volume (FVI x HR/renal cortex volume)
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Normal fetal kidney perfusion
cm/sec
Hindryckx et al. 2013, IPNA Poster P-SUN009
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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
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Pediatricians/pediatric nephrologists should be involved in prenatal follow-up of patients
with CAKUT!
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Acknowledgments
Katholieke Universiteit LeuvenAn Hindryckx Luc De CatteAnke Raaijmakers Djalila Mekahli Karel Allegaert
Inserm ToulouseJoost SchanstraStéphane DecramerJean-Loup Bascands
UCL University College LondonPaul Winyard
Universitätsklinikum HeidelbergFranz SchaeferElke WühlAnke Doyon
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THANK YOU!
Fons Sapientiae by Jef Claerhout
Leuven, Belgium
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Embriology of kidney development
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Song et al. Pediatr Nephrol 2011
Abnormal kidney development
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Molecular regulation of kidney development (1)
M. Little et al. Current Topics in Developmental Biology 2010
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Molecular regulation of kidney development (2)
Townes-Brocks syndrome
Denis-Drashsyndrome
Brachio-otorenal syndrome
Oculo-renaal syndrome
M. Little et al. Current Topics in Developmental Biology 2010
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Role of HNF1 beta in kidney development
Naylor et al. JASN 2013
Renal cysts – diabetes syndrome
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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
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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
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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 0.37-0.76) and specificity 0.84 (95% CI 0.71-0.94)
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AF 4-quadrant index