Renal Development Dysplasia 2

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Text of Renal Development Dysplasia 2

  • 1. Renal Development & Dysplasia Part I Hsiao Lai, MD Feb 19, 2010 ECU, Brody School of Medicine Nephrology and Hypertension Pediatric Nephrology Core Curriculum

2. Where will you encounter Renal Dysplasia?

  • Ob-Gyn referal prenatal screening ultrasound at 20wks
  • Neonatal nursery/NICU
    • Abnormal RUS
    • Congenital malformation syndrome with renal anomalies
    • Primary renal failure/insufficiency
  • Childhood:
    • Frequent UTIs
    • Incidental finding on abdominal imaging
    • Hypertensive child
  • Adolescent
    • Present in renal failure/ESRD requiring dialysis or transplantation

3. Congenital Anomalies ofKidney and Urinary tract(CAKUT)

  • Account for:
  • Diverse non-syndromic renal and lower urinary tract malformations
  • Most common congenital anomaly
  • 1/3 of all anomalies detected by routine fetal ultrasound (18-22 wk)
  • 40% of childhood ESRD

Woolf et. Al: in Renal Dysplasia Birth Defects Monitoring Program 4. Causes of Pediatric ESRD % 23 Other 3 PKD 3 Cystinosis 5 Nephronophthises 8 Congenital Nephrotic Syndrome 18 Acquired GN 40 CAKUT 5. Common Congenital Renal Anomalies

  • Cystic Dysplastic Kidneys
  • Renal agenesis
  • Horseshoe Kidney
  • Ectopic Kidneys
  • Duplicated Kidneys and Ureters

6. Common Urogenital Anomalies

  • Urinary Outlet Obstruction
    • Ureteropelvic Junction Obstruction UPJ
    • Ureterovesicle Junction Obstruction UVJ
    • Posterior Urethral Valves
    • Anterior Urethral Valves
    • Congenital Megaureter
  • Primary Vesicoureteral Reflux
  • Ureterocele

7. Congenital Renal Anomalies

  • Present at birth
  • Occur during the process of organogenesis
  • Involves defects:
    • Tissue Induction
    • Reciprocal feedback between tissue precursors
    • Morphogenesis
    • Migration

8. Intermediate mesoderm 9. Renal Development

  • Intermediate mesoderm
  • Pronephros
  • Mesonephros
  • Nephric (Wolffian) Duct formation
  • Metanephros = Fetal Kidney

10. Formation of Fetal Kidney

  • Wk 4: appearance of Wolffian or Mesonephric Duct
  • D28: formation of Ureteric Bud (UB)
  • Wk 4-8: Initial MM induction and UB branching
  • Week 8: First nephrons are formed
  • Week 4-8 kidneys ascend from pelvis to lumbar location
  • Wk 10 filtration begins

11. Renal and Urogenital Development

  • 1 st6-10 UB branches coalesce to form renal pelvis and calyces
  • Wk 5 implantation of distal UB into posterior urogenital sinus
  • Wk 5-7 ureter becomes occluded
  • Wk 7-8 recanalization of ureter

12. Urogenital Development

  • Wk 4-6: cloaca separates into anterior and posterior portion
  • Anterior cloaca develops into urogenital sinus which gives rise to the bladder and urethra
  • Posterior cloaca gives rise to the rectum
  • Urogenital sinus continuous superiorly with allantois which later regresses.
  • Expanded superior portion of urogenital sinus becomes the bladder
  • Inferior portion gives rise to pelvic urethra and also the penile urethra in males and the vestibule of the vagina in females

13. Later Stages of Nephrogenesis

  • In humans the early UB divisions are not associated with nephrogenesis
  • Wk 8-15 Period of UB branching with stochastic formation of UB ampulla and nephron units
  • UB branching decelerates after 15 wks, however nephron induction continues up until 32-26 weeks
  • Wk 15-20 Arcade induction of 5-7 nephrons per ampulla
  • Wk 20-36 Serial induction of without UB branching
  • Wk 32-36 End of Nephrogenesis

14. Late Nephrogenesis 15. Mechanisms of Maldevelopment

  • UB Agenesis
  • UB Duplication
  • Disruption of Renal Mesenchyme
  • Interrupted Cross-talk between UB and MM
  • Abnormal apoptosis/proliferation
  • Abnormal UB implantation
  • Abnormal UB recanalization
  • Abnormal renal migration

16. Edith Louise Potter

  • 1901-1993
  • Early training in Minnesota
  • Chicago Lying-In Hospital
  • Pioneer in understanding perinatal pathology of congenital malformations
  • Rh Factor and congenital hemolytic anemia
  • Pioneer in renal development

Euro J Pediatrics 1994 17. Potters Syndrome

  • Bilateral renal agenesis
  • Syndrome of findings: Oligohydramnios, Potters facies, skeletomuscular abnormalities, pulmonary hypoplasia resulting from a particular series of developmental events stemming from
  • Death usually from respiratory failure within minutes to hours of birth

18. Normal Kidneys 19. Dysplastic Kidneys

  • Small or large abnormally shaped kidneys
  • Immature/undifferentiated or metaplastic (abnormal) renal structures
  • May be associated with cysts in case of cystic dysplastic kidneys or complete agenesis of kidneys
  • If dysplasia is extensive, renal dysfunction may necessitate nephrologic care, including renal replacement therapy
  • Very little or no excretory function
  • Often associated with urogenital anomalies and reflux

20. Multicystic Dysplastic Kidney

  • Minimal to no functional renal parenchyma usually with primitive tubules and foci of cartilage
  • Kidney consists of groups of noncommunicating cysts with fibrous connective tissue
  • Bunches of grapes appearance

21. Multicystic Dysplastic Kidney

  • 1/2400 live births
  • Usually unilateral with ureteral atresia
  • Increase incidence of reflux incontralateral kidney
  • Often regress over several months to years and may account for many cases ofunilateral renal agenesis
  • Uncommonly, the kidney develops tumors or infection, and hypertension may develop
  • Most experts recommend observation, although some advocate removing these kidneys, especially if solid tissue is extensive or unusual appearing on ultrasonography

22. MCDK 23. ARPKD

  • 1 in 20,000 individuals
  • Cysts in Kidneys and Liver
  • PKD1 gene polycystin
  • Variable severity and presentation, but severe cases usually present in neonatal/infantile period with renal symptoms later cases present with liver-related symptoms

24. ARPKD

  • 30-50% mortality in newborn period mainly from in-utero oligohydramnios leading to pulmonary hypoplasia
  • If survive newborn period 1/3 need dialysis or transplantation by age 10
  • Kidneys can have rapid growth over the first few months
  • Mild cases present in late childhood or adolescent with symptoms of periportal fibrosis with gastric varicele bleeding and mild renal insufficiency

25. ARPKD Cortical cysts form in collectng duct 26. ADPKD on Fetal US 27. Radiographic Appearance ofARPKD vs ADPKD 28. ADPKD kennythekidney.com 29. Renal Hypoplasia

  • Inadequate ureteral bud branching causes an underdeveloped, small kidney with histologically normal nephrons Small well formed kidneys
  • Functional on renogram
  • If hypoplasia is segmental, hypertension can occur, and ablative surgery may be needed

30. Decreased Nephron Number

  • Number of nephrons more than doubles between 20 and 40 weeks
  • Majority of nephrons form during final third of gestation
  • Final nephron number can be highly variable between 230,000 to 1800,000
  • One branching generation may result in 30-35% less nephrons than wild type- usually undetectable phenotypes
  • Decreased nephron number is related to increased risk of hypertension and chronic kidney disease

31. Duplex Kidney and Ureters

  • ~15% of all live births
  • Incomplete fusion of upper and lower pole moieties can result incomplete or incomplete duplication of the collecting system
  • Two ureteric buds arise from the mesonephric duct, or if a single UB divides into two branches before it invades into the metanephrogenic blastema

32. Weigert-Meyer Law Upper Pole Moiety: obstructed Lower Pole Moiety: refluxes 33. Weigert-Meyer Law

  • Upper pole moiety: ureter inserts ectopically, inferomedial to normal site
  • Lower