Gu: Afip Non-Neoplastic Kidney - Congenital And Cystic Diseases

Front 1

More than __percent of abdominal masses in neonates are due to congenital anomalies of the kidney and urinary tract

Back 1

more than 50%

Front 2

Potter's Sequence (aka__)

Back 2

- aka oligohydraminos sequence
- beak-like nose
- low-set ears
- receding chin
- pulmonary hypoplasia
- abnormally bent lower extremities and contractures

Due to decreased or loss of normal cushioning amniotic fluid

Front 3

Pulmonary hypoplasia seen in Potter's sequence is due to __

Back 3

- lack of maturational stimulation provided by amniotic fluid
- chest wall compression due to lack of cushioning by amniotic fluid
- diaphram elevation by enlarged kidneys

Front 4

Renal agenesis

Back 4

- COMPLETE absence of any renal tissue
- unilateral or bilateral
- bilateral usually stillborn with Potter's sequence
- unilateral - at increased risk for development of renal failure later in life due to secondary focal segmental glomerulosclerosis (seen in the overworking compensating kidney)

Front 5

Major DDX for bilateral renal agenesis is __

Back 5

bilateral aplastic dysplasia
- very small amount of malformed renal tissue may not be apparent grossly and only found on micorscopic exam of the expected kidney site

- presence of any renal tissue, normal or dysplastic, rules out congenital renal agenesis

Front 6

Likely cause of renal agenesis is failure of the ___ to develop from the mesonephric duct

Back 6

- ureteric bud
- the ureteric bud arises from the mesonephric duct
- it induces differention of the metanephric blastema (part of the metanophros, the direct precursor to the kidney) into renal parenchyma

Front 7

Maternal risk factors for development of renal agenesis in a child are __, ___, and __

Back 7

- diabetes
- alcohol
- age < 18

Front 8

Renal hypoplasia is __

Back 8

reduction in renal mass due to too little genesis or NORMAL renal tissue

Front 9

Simple versus oligomeganephronic hypoplasia

Back 9

simple
- no histologic abnormalities, just too little renal tissue

oligomeganephronic
- marked compensatory hypertrophy due to overwork as a result of reduced number of nephrons

simple hypoplasia is rare compared to oligomeganephronic hypoplasia

Front 10

In renal hypoplasia, renal function is stable in early childhood, but -...

Back 10

may decline in late childhood and early adulthood due to secondary focal segmental glomerulosclerosis (proteinuria)

Front 11

Renal hypoplasia can be an ___ event or occur as part of a ___

Back 11

- isolated event
- part of a syndrome (renal-coloboma syndrome)

Front 12

coloboma (greek:___)

Back 12

- unfinished
- affects various parts of the eye

Front 13

renal dysplasia is ___

Back 13

- aberrant differentiation of renal parenchyma that does not proceed beyond the production of undifferentiated tubular structures surrounded by primitive mesenchyme
- +/- divergent differentiation too (heterotopia), such as cartilage

- abn tubular structures may develop into cysts (note: cysts are no required for the diagnosis of renal dysplasia)

Front 14

Patterns of renal dysplasia inlcude__

Back 14

- multicystic dysplasia
- aplastic dysplasia
- hypoplastic dysplasia
- obstructive dysplasia
- diffuse dysplasia

Front 15

Dysplastic kidneys can be large or small. Kidneys with multicystic dysplasia are usually __

Back 15

large!

Front 16

Most common cause of abdominal mass lesion in neonates (1 in 5,000 live births) is ___

Back 16

unilateral renal multicystic dysplasia

Front 17

Multicystic dysplasia is __ bilateral

Back 17

- multicystic dysplasia is rarely bilateral and usually NOT part of syndromic anomalies

versus

- diffuse dysplasia is usually bilateral and often occurs as part of a syndrome of congenital anomalies

Front 18

aplastic renal dysplasia results in a ___

Back 18

tiny rudimentary dysplastic kidney(s)
- small irregular nondescript islands of tissue in the retroperitoneal fat

Front 19

unilateral multicystic dysplasia may undergo involution overtime

Back 19

- distinction from aplastic dysplasia may not be possible in an adult without knowledge of the size of involved kidney during infancy

Front 20

Kidneys with multicystic dysplasia have a __ shape

Back 20

irregular, cystic shape
- lack the reniform shape
- variably sized cysts

versus

diffuse dysplasia
- maintains a reniform shape
with relatively uniform sized cysts throughtout BOTH kidneys

Front 21

hypoplastic dysplasia results in __

Back 21

- small, mishapen kidneys with multiple conspicuous cysts like multicystic dysplasia, but they are small rather than large

Front 22

Histologic hallmark of renal dysplasia

Back 22

- primitive tubules and ducts lined by cuboidal or columnar epithelium, surrounded by poorly differentiated mesenchymal tissue
- may see scattered foci of heterotopic tissue (cartilage, adipose, smooth muscle)

- cartilage is most often found in subcapsular area

Front 23

obstructive dysplasia is by definition associated with __

Back 23

congenital urinary tract obstruction
- often see hydronephrosis and bladder hypertrophy

Front 24

Glomerular epithelial hyperplasia, often seen with ___ dysplasia, should not be confused with ___

Back 24

- obstructive dysplasia
- not be confused with crescentic glomerulonephritis!! with crescent formation

Front 25

Diffuse cytsic dysplasia must be distinguished from __

Back 25

- autosomal recessive polycystic kidney disease
(radially oriented cysts versus the randomly oriented, more rounded cysts of diffuse cystic dysplasia)
- early-onset autosomal dominant PKD

Finding primitive mesenchyme and undifferentiated tubules between the cysts indicates dysplasia!

Front 26

Renal dysplasias result from abnormal ___

Back 26

metanephric differentiation
- genetic basis is variable

Front 27

multicystic dysplasia is __ familial

Back 27

- rarely familial!!
- probably not a genetic abnormality in most cases

versus
- aplastic and diffuse dysplasia are more often hereditary

Front 28

Most cases of multicystic and obstructive renal dysplasia are probably due to __

Back 28

- abnomralities in ureteric bud, ureters, and distal urinary tract
- rather than intrinsic abn of the metanephric blastema

Front 29

Prognosis:
- severe bilateral renal dysplasia
- unilateral renal dysplasia
- bilateral obstructive or hypoplastic dysplasia
- diffuse cystic dysplasia

Back 29

Prognosis:
- severe bilateral renal dysplasia
-- usually lethal due to pulmonary hypoplasia4
- unilateral renal dysplasia
-- may be asymptomatic
- bilateral obstructive or hypoplastic dysplasia
-- often with renal insufficiency and may progress to secondary hydroneprhosis and pyleonephritis
- diffuse cystic dysplasia
-- often a/w with other anomalies as well, which also influence the px
- large unilateral multicystic dysplastic kidney
-- may cause discomfort due to hemorrhage, infarction, or inflammation

Front 30

Autosomal dominant polycystic kidney disease (ADPKD)
- prevalence
- responsible for __ % of ESRD in USA
- ___ leading cause of ESRD following ___ and___

Back 30

- 1 in 200-1000 population
- 10%
- third leadind cause of ESRD following diabetes and HTN

Front 31

ADPKD symptoms usually develop by the ___ decade

Back 31

third to fourth decade
- 50% have ESRD by age 60

- however, can present at any age or may remain
asymptomatic

- patients develop HTN, bilateral flank or abd masses, sense of fullness, hematuria (including blood clots in urine), progressive renal failure

Front 32

ADPKD that presents in the first year of life usually leads to ___ in childhood

Back 32

ESRD

Front 33

Extrarenal manifestations of ADPKD inlcude:

Back 33

- cysts in liver, pancreas, spleen, meninges, seminal vesicles
- noncystic manifestations include :
- intracranial aneurysms (10%)
- mitral valve prolapse (20%)
- aortic root dilatation (uncommon)
- dissection of the thoracic aorta (uncommon)

Front 34

Hepatic cysts a/w ADPKD are usually __

Back 34

asymptomatic

Front 35

Renal cysts in ADPKD are usually:

Back 35

- filled with clear or yellow fluid (unless hemorrhagic)
- range 0.5 to 5.0 cm
- contents may be under pressure!!
- cysts present in cortex and medulla

Front 36

There is an increased risk for __ in ADPKD

Back 36

RCC!

Front 37

Cysts in ADPKD are usually lined by __

Back 37

- simple cuboidal to columnar to flat epithelium
- scattered areas of epithelial proliferation with multilayering and possibly polypoid projections are often seen
-- RCC can develop in these areas of hyperplasia

Front 38

As the cysts of ADPKD progressive and increase in size and number they ___

Back 38

compress and eventually replace the normal renal parenchyma

Front 39

Glomerular cysts can be seen in ADPKD

Back 39

- DDX glomerulocystic disease

Front 40

The histologic picture of ADPKD

Back 40

- multiple cysts
- atrophic changes
- chronic inflammation
- fibrosis
- hemosiderin pigment
- may see evidence of acute and chronic pyelonephritis

Front 41

ADPKD versus multiple, simple renal cysts
(DDX)

Back 41

- simple cysts are common acquired lesions
- usually in outer cortex, bulging the capsule
- lined by nondescript flat epithelium
- extreme expression of this is the acquired cysts a/w with ESRD maintained with chronic dialysis
- clinical context!!

- usually pts dialyzed for 5+ years or develop in end-stage kidneys that remain in transplant recipients
- kidneys are usually smaller (200g) than those of ADPKD (2-4 kg)
-

Front 42

Cysts arise from ___ in ADPKD versus only the __ in ARPKD

Back 42

ADPKD: arise from any part of the nephron, including the glomerulus (glomerular cysts)

ARPKD: arise only from the collecting ducts (no glomerular cysts)

This is important in the DDX of cystic renal disease in children

Front 43

DDX of a kidney with numerous cysts affecting multiple sites along the neprhon

Back 43

- ADPKD
- tuberous sclerosis
- VHL syndrome

Front 44

Acquired cystic kidney disease increases risk of RCC. T or F

Back 44

True!
- as with ADPKD, foci of epithelial hyperplasia may predispose to the formation of RCC

Front 45

ADPKD is usually inherited as an ___ trait

Back 45

autosomal dominant trait, but may arise as a spontaneous mutation

Front 46

85% (majority) of ADPKD is due to genetic abnormality in the ___ gene

Back 46

- PKD1 gene on chr 16
- PKD2 gene on chr 4 and PKD3 gene (15%)

- code for polycystin-1, polycystin-2, and polycystin-3, respectively

Front 47

Delayed in onset of symptoms in ADPKD may due to requirement of a

Back 47

- second hit (acquired disruption of the second allele before the germline mutation can lead to cyst formation in the kidneys or liver)

Front 48

ADPKD is a progressive disease

Back 48

- renal cysts increase in size and number with progressive loss of renal parenchyma

Front 49

Complications of ADPKD

Back 49

- HTN
- bacterial pyelo (cyst provide a safe haven)
- most important extrarenal: intracranial arterial anuerysms

Front 50

ADPKD pts have a __-fold increase of rupture of an intracranial arterial anuerysm

Back 50

5-fold

Front 51

ARPKD may present clinically in __

Back 51

- in utero
- later in childhood

Front 52

ARPKD is __ common than ADPKD

Back 52

- Less common ( 1/10,000 to 50,000 live births) versus ( 1/200 to 1,000)

Front 53

Most infants with ARPKD __

Back 53

- are stillborn or die in perinatal period due to pulmonary insufficiency secondary to pulm hypoplasia (olighydraminos and enlarged kidneys causing chest compression)

Front 54

Kidneys in ARPKD (gross)

Back 54

- markedly enlarged (bilateral and symmetric)
- enlongated cortical cysts, perpendicular to capsule (radial pattern)
- cysts in the medulla are more rounded

Front 55

Cysts of ARPKD, in infants that survive past the neonatal period, become __

Back 55

- rounded
- can make the DDX between ARPDK and early onset ADPKD more challenging
- ADPKD: see glomerular cysts and cysts arising along the nephron in multiple sites

Front 56

Almost all patients with ARPKD have some degree of __ in the liver

Back 56

- hepatic biliary dysgenesis (developmental arrest in bile duct formation)
- dilated bile ducts surrounded by fibrosis
- portal areas with expanded interconnecting bile ducts surrounded by fibrous tissue

Front 57

ARPKD: reciprocal relationship between severity of renal cystic disease and severity of hepatic fibrosis and survival

Back 57

- short survival (not beyond perinatal period)
-- renal cysts in 90% collecting ducts
-- mild hepatic fibrosis

- survive several months
-- cysts in about 50% collecting ducts
-- mild hepatic fibrosis

- minority of pts who survive longer than a few years
-- cysts in less than 25% of collecting ducts
-- moderate to severe hepatic fibrosis

Front 58

ARPKD is due to mutation in ___

Back 58

PKHD1 gene on chr 6
- codes for fibrocystin

versus

ADPKD: PKD1 gene on chr 16, PDK2 gene on chr 4, and PDK3 gene (polycystin-1,2,3)

Front 59

Primary glomerulocystic diesease

Back 59

- dx of exclusion: exclude the numerous other cystic disease that can have glomerular cysts as one component

- ADPKD (esp. early-onset)
- renal dysplasia (esp. syndromic diffuse cystic dysplasia and osbructive dysplasia)
- nephronophthisis-medullary cystic disease

Front 60

nephronophthisis-medullary cystic disease is a group of familial chronic tubulointersitial renal diseases; cysts predominate at the ___

Back 60

- corticomedullary junction

This is a group of progressive renal disorders that usually have their onset in childhood. The common characteristic is the presence of a variable number of cysts in the medulla, usually concentrated at the corticomedullary junction. Initial injury likely involves the distal tubules with tubular basement membrane disruption, followed by chronic and progressive tubular atrophy involving both medulla and cortex and interstitial fibrosis. Although the presence of medullary cysts is important, the cortical tubulointerstitial damage is the cause ofthe eventual renal insufficiency, and some prefer the term hereditary tubulointerstitial nephritis for this group.[

Front 61

Nephronophthisis is ___ while medullary cystic disease is ___

Back 61

Nephronophthisis: autosomal rescessive with early-onset renal failure

Medullary cystic disease is autosomal dominant, with late-onset renal failure

They are grouped together due to overlapping pathologic and clinical features

Patients with MCD often do not present until renal failure is present - histologically there will be cysts involving the medullary pyramids with no/little involvement of the cortex which shows evidence of atrophy

Four variants of this disease complex are recognized: (1) sporadic, nonfamilial (20%); (2) familial juvenile nephronophthisis (40–50%), inherited as an autosomal recessive disease; (3) renal-retinal dysplasia (15%), also an autosomal recessive disease, in which the kidney disease is accompanied by ocular lesions; and (4) adult-onset medullary cystic disease (15%), which shows an autosomal dominant inheritance.

As a group, this complex is now thought to be the most common genetic cause of end-stage renal disease in children and young adults.

Four variants of this disease complex are recognized: (1) sporadic, nonfamilial (20%); (2) familial juvenile nephronophthisis (40–50%), inherited as an autosomal recessive disease; (3) renal-retinal dysplasia (15%), also an autosomal recessive disease, in which the kidney disease is accompanied by ocular lesions; and (4) adult-onset medullary cystic disease (15%), which shows an autosomal dominant inheritance. As a group, this complex is now thought to be the most common genetic cause of end-stage renal disease in children and young adults.

Four variants of this disease complex are recognized: (1) sporadic, nonfamilial (20%); (2) familial juvenile nephronophthisis (40–50%), inherited as an autosomal recessive disease; (3) renal-retinal dysplasia (15%), also an autosomal recessive disease, in which the kidney disease is accompanied by ocular lesions; and (4) adult-onset medullary cystic disease (15%), which shows an autosomal dominant inheritance. As a group, this complex is now thought to be the most common genetic cause of end-stage renal disease in children and young adults.

The expected course is progression to terminal renal failure during a period of 5 to 10 years.
(contrast with medullary sponge kidney, which is a common often asymptomatic lesion, in adults)

Front 62

Nephronophthisis is associated with extrarenal manifestations, while medullary cystic disease is __

Back 62

- MCD is NOT!

Nephronophthisis is a/w
- retinitis pigmentosa (Senior-Loken syndrome)
- hepatic fibrosis
- skeletal defects
- cerbellar vermis aplasia

Front 63

Retinitis pigmentosa

Back 63

RP is typically thought of as a rod-cone dystrophy in which the genetic defects cause cell death (apoptosis), predominantly in the rod photoreceptors; less commonly, the genetic defects affect the RPE and cone photoreceptors. The phenotypic variation is very significant because over 100 genes can cause RP.

Histopathologic changes in RP have been well documented, and, more recently, specific histologic changes associated with certain gene mutations are being reported. The final common pathway remains photoreceptor cell death by apoptosis. The first histologic change found in the photoreceptors is shortening of the rod outer segments. The outer segments progressively shorten, followed by loss of the rod photoreceptor. This occurs most significantly in the mid periphery of the retina. These regions of the retina reflect the cell apoptosis by having decreased nuclei in the outer nuclear layer. In many cases, the degeneration tends to be worse in the inferior retina, thereby suggesting a role for light exposure.

The final common pathway in RP is typically death of the rod photoreceptors that leads to vision loss. As rods are most densely found in the midperipheral retina, cell loss in this area tends to lead to peripheral vision loss and night vision loss. How a gene mutation leads to slow progressive rod photoreceptor death can occur by many paths, as illustrated by the fact that over 100 gene mutations can lead to a similar clinical picture.

Cone photoreceptor death occurs in a similar manner to rod apoptosis with shortening of the outer segments followed by cell loss. This can occur early or late in the various forms of RP.

Front 64

Nephronophthsis-medullary cystic disease - gross

Back 64

- kidneys are normal to small
- advanced disease leads to small fibrotic kidneys
- 75% have 0.1 to 1.5 cm cysts mostly at the corticomedullary junction
- may NOT see cysts (not required for dx)

Front 65

DDX of prominent medullary cysts

Back 65

Nephronophthsis-medullary cystic disease
- cysts mostly at the corticomedullary junction (not at papillary tips)
- no calcifications

Medullary sponge kidney
- cysts at the papillary tips
- calcifications involving the cysts

Front 66

Nephronophthsis-medullary cystic disease involves defects in the ___ tubules

Back 66

distal tubules

Front 67

Location of defect:
ADPKD

ARPKD

Nephronophthsis-medullary cystic disease

Medullary sponge kidney

Back 67

ADPKD: any site along nephron

ARPKD: collecting ducts

Nephronophthsis-medullary cystic disease: distal tubules

Medullary sponge kidney: terminal collecting ducts in medullary pyramids

Front 68

Medullary sponge kidney is __

Back 68

congenital dilation of the terminal collecting ducts in the medullary pyramids

Front 69

Medullary sponge kidney is often__, so the true prevalence is __

Back 69

- asymptomatic
- unknown

Front 70

complications of medullary sponge kidney can include

Back 70

- nephrolithiasis
- infection
- hematuria

in the absence of complications there is a only mild concentrating and acification defects

Front 71

Kidneys in medullary sponge kidney are __ (gross)

Back 71

- usually normal size
- 0.1 to 0.8 cm cysts in the medullary pyramids, most numerous in papillary tips

- unilateral or bilateral
- can affect few or most pyramids within a kidney

- irregular calculi and/or blood clot can be found within cysts

Front 72

most cases of medullary sponge kidney are ___

Back 72

sporadic

Front 73

The DDX for kidneys with cysts arising in multiple sites along the nephrone (glomerular cysts and tubular cysts) should include___

Back 73

- tuberous sclerosis!!
- Note: there is a possibilty of coexisting ADPKD and TS

Front 74

Genes involved in tuberous sclerosis

Back 74

- TSC1 gene: chr 9, hamartin
- TSC2 gene: chr 16, tuberin

NOTE: the genes TSC2 (TS)and PKD1 (ADPKD) are adjacent to one another on chr 16

large mutations that disrupt both genes can lead to concurrent TS and severe early-onset ADPKD

Front 75

Von Hippel-Lindau syndrome is characterized by

Back 75

- hemangioblastoma of the CNS
- retinal angiomatosis
- renal cysts
- RCC
- pancreatic cysts
- pheochromocytoma

Front 76

VHL: more than half of the patients have renal cysts

Back 76

renal cysts:
- mutiple, bilateral, up to 5 cm
- scattered throughout kidneys
- cysts wall usually thin, can have epithelial hyperplasia with intracystic excrscences
- can have cystic RCC

Front 77

RCC a/w VHL is more often

Back 77

- multiple and bilateral and cystic

Front 78

Presence of multiple renal cysts with RCC points to a dx of __

Back 78

VHL
- acquired cystic disease a/w dialysis is another multiple cystic disease with RCC

Front 79

VHL is due to mutation in __

Back 79

- VHL gene on chr 3
- tumor suppressor gene