2-2. CAKUT. Elena Levtchenko (eng)

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  • 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
  • 6. 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)
  • 7. 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
  • 8. Prenatal  postnatal CAKUT diagnosis EUROSCAN study: Fetal US of 709,030 birth in 12 European Countries Wiesel et al. EJMG 2005
  • 9. Gynecological classification of antenatal hydronephrosis • Antenatal hydronephrosis: incidence 1-5% in general fetal population • Classification of Society of Fetal Urology
  • 10. “Pediatric classification” of antenatal hydronephrosis Bladder filling ? Grade 1-2 Grade 2-3 Grade 4
  • 11. Prognosis of antenatal hydronephrosis Lee et al. Pediatrics 2006. Meta-analysis of 1,645 studies -> 17 studies sufficient quality
  • 12. Termination of pregnancy N=50 (2008-2013) Hyndrickx & De Catte, IPNA 2013
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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%
  • 17. Klein et al. Sci Transl Med 2013: proteomics study of fetal urine to predict postnatal renal function in congenital lower urinary tract obstruction
  • 18. Klein et al. Sci Transl Med 2013
  • 19. 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
  • 20. 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
  • 21. Can standard prenatal examinations predict postnatal outcome of renal function? An Hindryckx Luc De Catte Prenatal imaging studies Anke Raaijmakers Postnatal follow-up
  • 22. 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
  • 23. 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
  • 24. 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)
  • 25. Reference curve for 3D renal volume ml Hindryckx et al. 2013, IPNA Poster P-SUN009
  • 26. 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
  • 27. Fetal kidney perfusion • Peak systolic velocity (PSV) • Flow velocity integral in renal vein correlated to kidney cortex volume (FVI x HR/renal cortex volume)
  • 28. Normal fetal kidney perfusion cm/se c Hindryckx et al. 2013, IPNA Poster P-SUN009
  • 29. 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
  • 30. Pediatricians/pediatric nephrologists should be involved in prenatal follow-up of patients with CAKUT!
  • 31. 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
  • 32. THANK YOU! Fons Sapientiae by Jef Claerhout Leuven, Belgium
  • 33. Embriology of kidney development
  • 34. Abnormal kidney development Song et al. Pediatr Nephrol 2011
  • 35. Molecular regulation of kidney development (1) M. Little et al. Current Topics in Developmental Biology 2010
  • 36. Molecular regulation of kidney development (2) TownesBrocks syndrome DenisDrash syndrome Brachiootorenal syndrome Oculorenaal syndrome M. Little et al. Current Topics in Developmental Biology 2010
  • 37. Role of HNF1 beta in kidney development Renal cysts – diabetes syndrome Naylor et al. JASN 2013
  • 38. 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
  • 39. 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
  • 40. 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)
  • 41. AF 4-quadrant index