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Renal Development Dysplasia 2
 

Renal Development Dysplasia 2

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  • Intermediate mesoderm on either side of the dorsal body wall/notochord gives rise to 3 successive nephric structures of increasingly advanced design
  • Pronephroi- nonfunctional segmental nephrotomes which develop in cervical region-represent a vestige of primitive kidneys seen in lower vertebrates, begin to appear at 24 days and regress in the fourth week Mesonephros – initial appearance of mesonephros and mesonephric duct at 25 days. Metanephric blastema and metanephric ducts appear at 28 days or end of week 4 Mesonephros develop in thoracic and lumbar regions during 4 th week, functional with complete but simple nephrons drained by the mesonephric (Wolffian Ducts) Nephric ducts grow caudally to open into the posterior wall of the primitive urogenital sinus by week 5 Metanephroi-definitive kidneys begin to form during 5 th week by induction of sacral intermediate mesoderm by UBs
  • UBs sprout from the distal end of the mesonephric duct by week 5

Renal Development Dysplasia 2 Renal Development Dysplasia 2 Presentation Transcript

  • Renal Development & Dysplasia Part I Hsiao Lai, MD Feb 19, 2010 ECU, Brody School of Medicine Nephrology and Hypertension Pediatric Nephrology Core Curriculum
  • 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 UTI’s
      • Incidental finding on abdominal imaging
      • Hypertensive child
    • Adolescent
      • Present in renal failure/ESRD requiring dialysis or transplantation
  • Congenital Anomalies of Kidney 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
  • Causes of Pediatric ESRD % 23 Other 3 PKD 3 Cystinosis 5 Nephronophthises 8 Congenital Nephrotic Syndrome 18 Acquired GN 40 CAKUT
  • Common Congenital Renal Anomalies
    • Cystic Dysplastic Kidneys
    • Renal agenesis
    • Horseshoe Kidney
    • Ectopic Kidneys
    • Duplicated Kidneys and Ureters
  • 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
  • Congenital Renal Anomalies
    • Present at birth
    • Occur during the process of organogenesis
    • Involves defects:
      • Tissue Induction
      • Reciprocal feedback between tissue precursors
      • Morphogenesis
      • Migration
  • Intermediate mesoderm
  • Renal Development
    • Intermediate mesoderm
    • Pronephros
    • Mesonephros
    • Nephric (Wolffian) Duct formation
    • Metanephros = Fetal Kidney
  • 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
  • Renal and Urogenital Development
    • 1 st 6-10 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
  • 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
  • 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
  • Late Nephrogenesis
  • 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
  • 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
  • Potter’s Syndrome
    • Bilateral renal agenesis
    • Syndrome of findings: Oligohydramnios, Potter’s 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
  • Normal Kidneys
  • “ 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
  • 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
  • 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 of unilateral “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
  • MCDK
  • 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
  • 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
  • ARPKD Cortical cysts form in collectng duct
  • ADPKD on Fetal US
  • Radiographic Appearance of ARPKD vs ADPKD
  • ADPKD kennythekidney.com
  • 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
  • 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
  • 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
  • Weigert-Meyer Law Upper Pole Moiety: obstructed Lower Pole Moiety: refluxes
  • Weigert-Meyer Law
    • Upper pole moiety: ureter inserts ectopically, inferomedial to normal site
    • Lower pole moiety: ureter inserts orthotopically-posterio-lateral insertion into bladder trigone
    • Ectopic insertion often has a urethrocele which obstructs its own collecting system and can distort the lower moiety insertion and cause reflux into lower pole moiety
  • Duplex Kidney and Ureters
    • Complete duplication results when two entirely separate ureters drain separate upper and lower pole or two individual kidneys
    • Partial duplication occurs when the two ureters join before reaching the bladder
    • Duplication of the renal pelvis alone can also occur
  •  
  • Abnormalities of Renal Fusion, Ascent and Rotation
    • Horseshoe Kidney
    • Cross-fused Ectopia
    • Pelvic Kidney
    • Pancake Kidney
  • Abnormalities of Ascent and Rotation Horseshoe kidney Cross fused ectopia
  • Horseshoe Kidney
    • 1 in 400 live births
    • Kidneys fuse together early during ascent usually at lower poles
    • Connecting isthmus can be renal parencyhmal or fibrous tissue
    • Ureters usually drain medially and anteriorly to isthmus
    • Asymptomatic in the majority of cases
    • May be associated with reflux nephropathy if ureters implant more superiorly that causes CKD, or with more complex developmental syndromes
  • Crossed-Fused Ectopia
    • Kidneys fuse early in development
    • Both fused kidneys lie on one side of the spine, and the ureters cross the midline in order to enter the bladder with upper ureter implanting posteriorly
    • Often the upper kidney is obstructed, while the lower ureter refluxes
  • Pelvic/Ectopic Kidney
    • Kidney fails to ascend to normal location in the renal fossa
    • Predominantly pelvic location, rarely thoracic
    • Incidence is 1/900 live births, more commonly on left
    • Usually clinically asymptomatic and found coincidentally
    • Often associated with genital anomalies, but cardiovascular and skeletal anomalies are also common
    • 1/3 of siblings affected
    • Likely AD inheritance with widely variable penetrance
    • Structural abnormality of vesicoureteral junction with abnormally short submucosal segment of the ureter or deficiency in the musculature of the intravesical ureter
  •  
  • Bladder Outlet Obstruction
    • UPJ
    • UVJ
    • PUV
    • Ureteral Duplication
    • Ectopic Ureters
    • Congenital Megaureter
  • UPJ Obstruction
    • Most common upper urinary tract obstruction in children
    • Incidence 1/1000-1/2000 newborns
    • Most common cause of pediatric hydronephrosis
    • Account for 50% of hydronephrosis on prenatal ultrasound
    • More commonly on left, 20-30% bilateral
    • Often associated with other congenital anomalies especially MCDK
  • UPJ Obstruction
    • UPJ is formed during Wk 5 of gestation
    • The UPJ is the last area of the UB to recanalize
    • Abnormal or incomplete recanalization of the UB during development leads to UPJ obstruction
    • UPJ functional obstruction can also result from an aperistaltic portion of UPJ
  • UPJ Obstruction
  • Posterior Urethral Valves
    • Occurs only in males
    • 1/5000 male births
    • Most common cause of urinary tract obstruction in males
    • Accounts for 20% of all childhood ESRD
    • Wide range of severity with mild disease often missed until presentation with renal failure in adolescence, severe disease can present with Eagle Barrett Syndrome
  • Posterior Urethral Valves
    • Results from persistent obstructing urogenital membrane
    • Disrupted embryological development of male urethra between Wk 9-14
    • There seems to a also a component of renal dysplasia along with obstruction that does not necessarily resolve with correction of obstruction
  • PUV
  • Management PUV
    • Foley catheter decompression at birth
    • Management of associated renal dysfunction
    • Valve ablation within weeks of birth
    • Management of post ablation urinary incontinence
    • Monitor for VUR and CKD
    • Supravesical diversion prior to 21 wks, has not proved very successful
  • Congenital Syndromes with Renal Anomalies
    • Many widely diverse syndromes
    • Not enough time to summarize here
    • Maybe a later presentation?
    • Enjoy your weekend!