Embryology of kidney, anomalies of number, anomalies of ascent, anomalies of form and fusion

1. Presented by
Rojan Adhikari
Resident
EMBRYOLOGY OF
KIDNEY
URETER

2. OBJECTIVES
• Stages of Kidney Development
• Development of Nephron
• Development of the Collecting System
• Development of Ureter
• Applied Aspects
- Abnormalities in number
- Abnormalities of ascend
- Abnormalities of form and fusion

4. Basic Concepts
The 3 embryonic germ layers

5. Embryologically, all three kidneys develop from the intermediate mesoderm.

6. Mammalian Kidney Development
UROGENITAL
RIDGE

7. Stages of Kidney Development

8. Pronephros
• PRONEPHROS develops
from the cranial most
part of urogenital ridge.
• It is transitory and
regresses completely by
5 weeks of gestation
• It is non functional in
Humans.

9. Mesonephros
• MESONEPHROS
develops caudal to
the Pronephros.
• It consists of a series of
tubules that drain into
the nephric duct,
which can be called
the Mesonephric duct.
• Excretory organ for
embryo until
metanephros takes
over.

10. METANEPHROS, third and
final stage of Kidney
development
- It results from Reciprocal
inductive signals between the
Metanephric Mesenchyme and
the Ureteric Bud at the caudal end
of the Urogenital bridge.
-Ureteric bud is an outgrowth at
the distal end of the Wolfian duct,
first visible at approx. 5 weeks of
gestation.
Metanephros

11. METANEPHROS

12. • The metanephric mesenchyme induces the
ureteric bud to branch and divide, and in turn
the ureteric bud induces the metanephric
mesenchyme to condense and undergo
mesenchymal epithelial conversion.
• Metanephric mesenchyme : The nephron,
(glomerulus, proximal tubule, loop of Henle,
and distal tubule)
• Ureteric bud : collecting system, consisting of
collecting ducts, calyces, pelvis, and ureter,

14. Development of Nephron
• Metanephric mesenchyme
(MM) becomes distinct from
the surrounding loose
mesenchymal cells and come
to lie adjacent to the Ureteric
bud (UB)
• Upon invasion of UB in the loose
MM, signals from MM cause UB
to branch into a T - tubule

15. • Renal Vesicle in contact with the epithelium of the ureteric bud
forms the ‘COMMA SHAPE’
• Glomerulus develops from the most proximal end of the Renal
Vesicle.
• These cells also develop into Podocytes.
• Vascular cleft develops between podocyte layes and the more
proximal cells – ‘S SHAPE’
• Endothelial cells migrate into the vascular cleft

16. Schematic representation of progressive nephron
differentiation.

17. Development of the Collecting
System
• The collecting ducts are all derived from the Ureteric Bud
• By 20 to 22 weeks, ureteric bud branching is completed
• This branching is highly patterned

18. The ureteric bud initially penetrates the metanephric mesoderm,
and then undergoes repeated branching to form the
• ureters,
• renal pelvis,
• major calyces,
• minor calyces, and
• collecting ducts

19. Renal Ascent
• The fetal metanephros is
located at vertebral level
S1-S2, whereas the
definitive adult kidney is
located at vertebral level
T12-L3.
• From 6th to 9th weeks:
kidneys ascend to a
lumbar site just below
adrenals

20. Development of Ureter
• At the fifth week of development, the ureteric bud arises as a
diverticulum from the mesonephric duct.
• The bud grows laterally and invades the center of the
metanephrogenic mesenchyme
• Later mesonephric duct get absorbed within the cloaca and
ureteric bud directly opens into the cloaca,

22. Abnormalities of Number
Dysgenesis of the Kidney
Renal Agenesis (absent Kidney) : Failure of the ureteral bud to
communicate with the
metanephric blastema
UNILATERAL BILATERAL

23. Unilateral Renal Agenesis
• Incidence 1:1100
• Males predominate with a ratio of
1.8 : 1.
• The ipsilateral ureter is completely
absent in about half of the patients
• About 90% single kidney undergo
compensatory hypertrophy in utero
from 20 weeks’ gestation (Van Vuuren et
al, 2012).

24. Bilateral Renal Agenesis
• Incidence 1: 4800 births
• A total of 40% of the affected infants are stillborn.
• Most of the children who are born alive do not
survive beyond 48 hours because of respiratory
distress associated with pulmonary hypoplasia.

25. Bilateral Renal Agenesis
• The characteristic Potter
facies and the presence
of oligohydramnios are
pathognomonic.

26. • Two metanephros develop
only after being penetrated by
the bifid or separate Ureteric
bud.
• The supernumerary kidney
may be either completely
separate or loosely attached to
the kidney on the ipsilateral
side.
Supernumerary Kidney

27. ANOMALIES OF ASCENT

28. Simple Renal Ectopia
• Incidence varies from 1 : 500
to 1 : 1200
• The left side is affected
slightly more than the right.
• Most ectopic kidneys are
clinically asymptomatic

29. Cephalad Renal Ectopia
• The kidney may be positioned more cranial than normal
• Associated with omphalocele
• The ureters were excessive in length

30. ANOMALIES OF FORM AND FUSION
Fusion anomalies of the kidney were categorized as
A. Crossed ectopia with fusion,
B. Crossed ectopia without fusion,
C. Solitary crossed ectopia, and
D. Bilaterally crossed ectopia

35. Horseshoe Kidney
• It is due to fusion of mesonephric duct.

36. THANK YOU

37. • Anomalies of rotation
• Anomalies of Renal Vasculature
• Anomalies of collecting system
• Renal Dysgenesis and
• Cystic Disease of the Kidney

39. Congenital Anomaly of
kidney
Presented by
Rojan Adhikari
Urology Resident

41. Anomalies of rotation
Incidence. 1 : 939 autopsies, Campbell (1963) and
1 : 390 hospital admissions Smith and Orkin (1945)
It is frequently observed in association with
Turner syndrome (Gray and Skandalakis, 1972b).
Males > females,

42. Primitive embryonic position;
hilus faces ventrad (anterior)
Normal adult position; hilus faces medial
Incomplete rotation
Hyper-rotation; hilus faces dorsad (posterior) Hyper-rotation; hilus faces laterad Reverse rotation; hilus faces laterad.

43. Normal Kidney Transverse view of malrotated right kidney. Note the
anterior position of the renal pelves (arrows).

44. ANOMALIES OF RENAL VASCULATURE
Aberrant, Accessory, and Multiple
Vessels
• Failure of involution of
arteries during ascent
• Incidence : Around 25 %
population

45. Embryology
During renal migration the network of vessels selectively
degenerates, and the remaining adjacent arteries assume a
progressively more important function.

46. Renal Artery Aneurysm
Incidence between 0.1% and 0.3%
90% are smaller than 2 cm
Right > Left
Bilateral aneurysms are seen in 15%
Renal artery aneurysms is classified by Abeshouse
(1951) as saccular, fusiform, dissecting, and
arteriovenous

47. Rundback et al
• Type 1 : Saccular aneurysms
• Type 2 : Fusiform aneurysms
• Type 3 : Intralobar aneurysms

49. Renal Arteriovenous Fistula
25% of all AVFs are
congenital
Loud bruit in 75% of cases &
hypertension in approximately
50%
Macroscopic and microscopic
hematuria occurs in more than
75% of affected individuals

50. ANOMALIES OF THE COLLECTING SYSTEM
Calyceal Diverticulum
Incidence 4.5 per 1000 on excretory
urography
Embryologic , ureteral branches of
the third and fourth generation, which
ordinarily degenerate, may persist as
isolated branches, resulting in the
formation of a calyceal diverticulum
Sequence of coronal T2 images showing Lower pole calycea
diverticulum.

52. CONGENITAL MEGACALYCES
Males : Female : 6:1
Bilateral only in male
Embryology: The transient delay in
recanalization of the upper ureter after the
branches of the Ureteric bud hook up with
the metanephric blastema. This produces
transient obstruction causing megacalyces

54. URETEROPELVIC JUNCTION OBSTRUCTION
•Congenital obstruction of the UPJ is a common
anomaly of urinary tract.
• Incidence is 1 in 500 live births
•Males : female 2:1, Left sided
•Embryologic disruption of the proximal ureter that
alters circular musculature development and/or
collagen fibers
•Commonly presents as an abdominal mass in a
neonate.

55. Renal dysplasia
Dysplasia is a histologic diagnosis made
by the presence of embryonic, immature
mesenchyme, and primitive renal
components
primary cause of childhood ESRD
Associated with ureteric bud anomalies
and/or urinary tract obstruction.
Ultrasonographic appearance of renal dysplasia.

56. Renal Hypoplasia
Smaller size and deficiency in
the number of cells/glomeruli
Types:
1. Unilateral
2. Bilateral: CRF
3. Segmental hypoplasia
May be bilateral or unilateral.
In unilateral cases, the other
kidney usually shows greater
compensatory growth

57. CYSTIC DISEASES OF THE KIDNEY
INHERITABLE
Autosomal recessive (infantile) polycystic kidney disease
Autosomal dominant (adult) polycystic kidney disease
Medullary cystic disease (autosomal dominant)
Multiple malformation syndromes with renal cysts (e.g., tuberous sclerosis, von Hippel-Lindau disease)
NONHERITABLE
Multicystic kidney (multicystic dysplastic kidney)
Benign multilocular cyst (cystic nephroma)
Simple cysts
Medullary sponge kidney

58. Autosomal recessive (infantile) polycystic kidney disease
Incidence varies from 1 in
10,000 to 50,000 live births
50% of affected newborns die
in the first few days of life
Cysts derived principally from
collecting duct

59. ARPKD

60. Autosomal dominant polycystic kidney
disease (ADPKD)
Incidence of approximately 1 in 400
to 1000 live births
ADPKD most often becomes
clinically apparent after age 30 years
Microcysts and macrocysts derived
from the entire nephron
.

61. ADPKD

62. Medullary cystic disease
Multiple cysts in the medulla and
corticomedullary junction
Inherited in an autosomal dominant pattern
Slowly progressive kidney disease due to
progressive interstitial fibrosis

63. Medullary cystic disease

64. Multicystic dysplastic kidney (MCDK)
Multiple cysts of varying sizes, without
identifiable normal renal parenchyma
Incidence is 1 per 1000 to 4000 live births
Most common type of renal cystic disease
in infants
Male preponderance (55% to 70%),
A typical multicystic dysplastic kidney having the
appearance of a bunch of grapes. The kidney is
composed almost entirely of cysts with very little
stroma

65. MCDK

66. SIMPLE CYSTS
Simple cysts are the most common cystic lesions found in the
human kidney
Incidence
 Birth to 18 years : 0.22%
 At 40 years: 20% and
 After 60 years : >50%

68. Bosniak’s Classification
CATEGORY
I
• Bosniak suggested a classification
in 1986 that was clarified further in
1997
• Modified by Israel and Bosniak in
2003

69. CATEGORY II

70. CATEGORY II F

71. CATEGORY III

72. CATEGORY IV

74. MEDULLARY SPONGE KIDNEY
Incidence 1 : 200 among patients undergoing
intravenous urography
Usually B/L may be unilateral or segmental.
Autosomal dominant inheritant
Embryology: disruption at the ureteric bud–
metanephric blastema or RET/GDNF interface
Associated with hypercalciuria

76. THANK YOU

79. Molecular Mechanism of Kidney
Development
• Formation of renal tubules and the collecting system occurs
sequentially and requires dynamic interactions among epithelial,
mesenchymal, and stromal cells.
• Grobstein’s in 1956 led to an organ culture technique and found
that metanephric mesenchyme is separated from the ureteric bud
during the early part of kidney development and grown in vitro
on a filter.
• An inducer tissue, such as ureter or spinal cord, cultured on the
opposite side of the filter then provides the inductive signal

80. Schematic representation of (A) in vivo kidney development and
(B) An in vitro transfilter organ culturesystem of Grobstein

81. • Glial cell line–derived
neurotrophic factor (GDNF) is
secreted from the metanephric
mesenchyme and activates the
RET receptor tyrosine kinase in
the ureteric bud epithelium.
• The inducibility of nephric
ducts to GDNF signaling is
restricted by the action of bone
morphogenetic protein-4
(BMP4). Inductive interactions during early kidney
development.

82. Cell-cell interactions promote nephrogenesis
• Wnt4 is activated in the
tubular mesenchymal cells by
the invading UB epithelial
cells and stimulates the
development of polarized
epithelium in an autocrine
fashion.
• Fibroblast growth factors
(FGFs), such as FGF2, along
with leukocyte inhibitory
factor (LIF), may be critical as
survival factors for the
developing renal tubular
epithelial cells.

83. DEFECTS IN SIGNALING
• Defect of Eya1 results in a dominantly inherited disorder called
branchio-oto-renal syndrome, which involves kidney and
urinary tract anomalies (Abdelhak et al, 1997).
• Pax2 mutation exhibit decreased ureteric bud branching and
renal hypoplasia (Porteous et al, 2000).
• Mutations in either Fox gene result in an expansion of GDNF
expression and the formation of ectopic ureteric buds.

84. • FoxC1 homozygous mutants have duplex kidneys, in
which the upper ureter is dilated (Piper et al, 2000)
• mutation of Sall1 exhibit developmental arrest
(Nishinakamura et al, 2001).
• Mutations of Pax2 or Wt1 fail to exhibit ureteric bud
outgrowth, and in both cases the metanephric mesenchyme
does not respond to induction (Kreidberg et al, 1993;
Brophy et al, 2001).
• WT1 is a transcription factor originally identified as a
gene involved in Wilms tumor, a pediatric cancer in which
kidney elements are incompletely differentiated and
proliferate to form tumors.