Renal Embryology

Question 1

renal development - general concepts

Answer 1

*developing fetus has an intermediate mesoderm (IM) which develops craniocaudally from the cervical to lumbar regions of the fetus
*mammals develop 3 pairs of embryonic kidneys sequentially: 1) pronephros; 2) mesonephros; 3) metanephros

Question 2

renal development - tissues

Answer 2

*at 5 weeks gestation, reciprocal signaling induces the outgrowth of the ureteric bud from the caudal mesonephric duct
*metanephric mesenchyme condenses around the ureteric bud to become metanephric blastema

Question 3

renal development - timeline

Answer 3

*4 wks gestation: kidneys start developing
*9wks: first glomeruli, bladder
*20-36 wks: nephrogenesis occurs
*~36 wks: nephrogenesis is complete
*at birth, kidney growth is due to enlargement of the glomerular diameter & significant increase in tubular volume and length

Question 4

nephrogenesis

Answer 4

1. vesical differentiates and elongates, forming a comma-shaped, then S-shaped body
2. the lower limb of the S-shaped body forms the glomerular podocytes
3. endothelial cells migrate into the cleft of the S-shaped body
4. the distal end of the S-shaped body elongated and differentiates to from nephron tubules from the proximal tubule to the DCT
5. DCT connects to the collecting system

Question 5

ureteric bud/mesonephric duct differentiate into

Answer 5

COLLECTING SYSTEM:
*ureter
*renal pelvis
*major and minor calyces
*collecting tubules & ducts
*Trigone of bladder

Question 6

metanephric blastema differentiates into

Answer 6

NEPHRONS:
*podocytes
*epithelial cells lining Bowman’s Capsule
*proximal convoluted tubules
*loop of Henle
*distal convoluted tubules

Question 7

effects of prematurity on renal development

Answer 7

*human nephrogenesis stops at birth
*therefore, premature infants have REDUCED NEPHRON MASS
*leads to increased risk of hypertension, chronic kidney disease

Question 8

congenital anomalies of the urinary system (overview)

Answer 8

*renal anomalies are common, 3-20% of live births
*many asymptomatic
*may not manifest until later in life
*causes include: environmental factors (maternal medication exposure, high glucose, folate deficiency) or genetically based
*more than 500 syndromes with genetic basis that involve malformations of the urinary tract

Question 9

renal duplications

Answer 9

*embryonic anomaly = bifurcation or duplicated ureteric bud
*results in extra ureter
*ectopic expression of GDNF by metanephric mesenchyme more proximally along mesonephric duct

Question 10

renal agenesis - overview

Answer 10

*embryonic anomaly = faulty interaction between ureteric bud and metanephric mesenchyme
*attributed to mutations of glial cell line-derived neurotrophic factor (GDNF), which plays a role in induction of the ureteric bud

Question 11

unilateral renal agenesis

Answer 11

*solitary kidney; remaining kidney undergoes compensatory enlargement, such that most patients are asymptomatic
*occurs in 0.1% of adults
*high rate of coexisting urogenital abnormalities

Question 12

bilateral renal agenesis

Answer 12

*incompatible with extra-uterine life
*results in oligohydramnios, no kidneys, and non-visualized bladder on prenatal ultrasound
*one of the causes of Potter Sequence

Question 13

Potter Sequence - pathogenesis

Answer 13

*oligohydramnios → compression of developing fetus → limb deformities, facial anomalies (low-set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death)

Question 14

Potter Sequence - etiology

Answer 14

*caused by chronic placental insufficiency or reduced fetal urine output (oligohydramnios), including:
-ARPKD
-obstructive uropathy (ex. posterior urethral valves)
-bilateral renal agenesis

Question 15

Potter Sequence - clinical presentation

Answer 15

P - pulmonary hypoplasia
O - oligohydramnios
T - twisted face
T - twisted skin
E - extremity defects
R - renal defects

Question 16

renal hypoplasia

Answer 16

*unilateral OR bilateral
*SMALL size, non-dysplastic, less than normal number of nephrons
*can lead to chronic kidney disease if bilateral
*genetic causes, maternal factors

Question 17

renal aplasia

Answer 17

*rudimentary kidney

Question 18

renal dysplasia

Answer 18

*embryonic anomaly = abnormal metanephric differentiation
*unilateral or bilateral
*kidney(s) often contain ectopic tissue (cartilage, muscle)
*kidneys may have cysts
*reduced renal function, more likely to develop chronic kidney disease
*can occur with renal hypoplasia

Question 19

multicystic dysplastic kidney (MCDK)

Answer 19

*embryonic anomaly = abnormal metanephric differentiation
*MOST COMMON CAUSE OF CONGENITAL SOLITARY KIDNEY
*60% involute by age 10 yrs
*second most common cause of flank mass in newborn
*usually UNILATERAL (bilateral not compatible with life)
*2x more common in MALES
*kidney is not functional
*atretic ureter
*detected during antenatal ultrasound

Question 20

congenital polycystic disease

Answer 20

*hundreds to thousands of cysts within kidney parenchyma
*cysts form from variety of locations along nephron
*other organs (pancreas, liver) can be involved
*includes ADPKD, ARPKD, and medullary cystic kidney disease

Question 21

effects of fetal exposure to RAAS blockade (ACEi or ARB)

Answer 21

*few infants survive
*results in oligohydramnios
*after neonatal period: polyuria, polydipsia
*salt-losing nephrogenic diabetes insipidus
*inability to concentrate urine due to impaired osmotic gradient in renal medulla
*reduced glomerular filtration rate

Question 22

hydronephrosis - overview

Answer 22

*most common cause of ABDOMINAL MASS IN NEWBORN
*dilation of renal pelvis & collecting system
*diagnosed on antenatal ultrasound or incidental finding post-natally
*dilation of renal pelvis and between renal calyces
*can be unilateral or bilateral

Question 23

Alport Syndrome

Answer 23

*inherited disorder, due to mutation of genes encoding alpha-3, -4, or -5 type IV collagen chains (most commonly X-linked), resulting in abnormal basement membrane (basket-weave appearance)

*clinical manifestations:
-hematuria
-proteinuria
-progressive CKD → renal failure
-sensorineural hearing loss
-ocular abnormalities (lens displacement anterior lenticonus)

Question 24

hydronephrosis - causes

Answer 24

1. vesicoureteral reflux
2. obstruction (UPJO, PUV, or ureterovesical junction obstruction)
3. transient/physiological
4. neurogenic bladder

Question 25

ureteropelvic junction obstruction (UPJO)

Answer 25

***complete or partial obstruction of the ureter where it exits the kidney** (between the renal pelvis and the ureter) *mostly arises from a congenital stenosis of the ureter *detected antenatally *common cause of hydronephrosis (bear paw pattern) *presenting symptoms: flank mass, UTI, pain, hematuria

Question 26

vesicoureteral reflux (VUR) - overview / epidemiology

Answer 26

***retrograde flow of urine from bladder toward upper urinary tract** *most common pediatric urologic condition *affects up to 30% of children with a febrile UTI *common cause of hydronephrosis, but does not always present with hydronephrosis *often self-resolves as child grows *can be a secondary VUR due to high bladder pressure (neurogenic bladder, posterior urethral valves) *complications include **chronic UTIs, pyelonephritis, renal scarring, HTN, chronic kidney disease**

Question 27

vesicoureteral reflux (VUR) - defined

Answer 27

*retrograde flow of urine from the bladder back into the ureters, and sometimes all the way up to the kidneys

Question 28

primary vesicoureteral reflux (VUR) - pathogenesis

Answer 28

*malformation of the ureter as it passes through the bladder wall, preventing normal closure of the ureter at the ureteric opening into the bladder *usually corrects itself or improves with aging

Question 29

secondary vesicoureteral reflux (VUR) - pathogenesis

Answer 29

*urine flow distal to the ureters is obstructed, usually either in the bladder neck or in the urethra *commonly caused by posterior urethra valves in males

Question 30

vesicoureteral reflux (VUR) - complications

Answer 30

*increased risk of urinary tract infections, including pyelonephritis *scarring, HTN *increased risk of CKD *reflux nephropathy due to chronic urine reflux back into the kidney

Question 31

lower urinary tract development

Answer 31

*the cloaca gives rise to the bladder and the lower GI tract (rectum & anus) *at 4-5 weeks gestation, the cloaca divides into the anterior urogenital sinus and the posterior anal canal *superior portion of urogenital sinus → urinary bladder *middle portion of urogenital sinus → prostatic & membranous portions of the urethra

Question 32

bladder exstrophy

Answer 32

*embryonic anomaly = **failure of abdominal wall to close during fetal development** *results in protrusion of posterior bladder wall through the lower abdominal wall *symphysis pubis diastasis *multiple abnormalities in pelvis, bladder, urethra, and external genitalia *common in males *associated abnormalities: vesicoureteral reflux, incontinence, recurrent UTIs, hernia

Question 33

posterior urethral valve (PUV) - overview

Answer 33

*most common cause of URINARY OBSTRUCTION IN MALE children ***congenital valve in the posterior (prostatic) urethra due to persistent urogenital membrane** *important b/c they can obstruct urine flow *associated with renal dysplasia *spectrum of severity *risk of perinatal mortality & HIGH risk of chronic kidney disease

Question 34

posterior urethral valves (PUVs) - pathogenesis

Answer 34

*a congenital malformation of the prostatic urethra caused by **persistence of urogenital membrane** (only present in males)

Question 35

posterior urethral valve (PUV) - postnatal presentations

Answer 35

*pulmonary hypoplasia *weak urine stream *frequent UTI *voiding dysfunction, enuresis (incontinence) *trouble toilet training

Question 36

Prune Belly Syndrome / Triad Syndrome

Answer 36

*triad of: 1. deficiency or absence of anterior abdominal wall musculature 2. bilateral cryptorchidism (undescended testicles) 3. bilateral ureter, bladder, & urethral abnormalities

Question 37

ectopic kidney

Answer 37

1. pelvic kidney (most common): -failure of kidney to ascend during embryogenesis, resulting in kidney remaining in pelvis 2. cross-fused ectopia: -one kidney and its ureter are on the same side of the body as the other kidney -may be fused with normal kidney *associated anomalies: VUR most common

Question 38

horseshoe kidney - overview

Answer 38

*fusion abnormality in which the kidneys are fused together, typically at the lower poles *isthmus of horseshoe kidney lies at the level of L4-L5 (gets trapped on **inferior mesenteric artery** during ascent) *more susceptible to trauma due to blockage of inferior mesenteric artery *more common in: males, Turner Syndrome, Trisomy 18 *complications: 50% associated with VUR; increased risk of ureter obstruction

Question 39

horseshoe kidney - pathogenesis

Answer 39

*the two kidneys fuse (usually the lower poles) during development *when the poles migrate upward during growth, the fused midline portion becomes **trapped at the inferior mesenteric artery,** placing the fused kidneys lower in the abdomen and less protected than usual