Congenital Anomalies of Kidney and Lowe Urinary Tract
Congenital Anomalies of kidney
Clinical
Presentation
Agenesis of Kidney
Hypoplasia
Bilateral:
- incompatible with life
- encountered in stillborn infants
- associated w. limb defect and
Hypoplastic lungs
- Bilateral→renal failure - Predisposes it to bacterial
Unilateral agenesis:
- uncommon
- Unilateral: compatible with life if
no other abnormalities exist
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-
Ectopic Kidneys
in childhood
Unilateral common
True renal hypoplasia
observed in Low Birth
infants
Increased lifetime risk
for CKD
Congenital Anomalies of Ureters
Congenital Anomalies of the Bladder
Horseshoes kidneys
Double & Bifid Ureters
Ureteropelvic Junction obstruction
Diverticula
Vesicuretral reflux
Diverticula of the bladder
Exstrophy of Bladder
- 1 in 500 to 1000 autopsies
- most unilateral; no clinical significance
- congenital disorder that commonly
- uncommon lesions
- Congenital or acquired
- Most asymptomatic but
- most common
- Serious congenital anomaly of
- Predispose infection and formation of
- risk for infections that spread to - carcinoma
infection bc of abnormal
position, kinking or tortuosity
of ureters that causes
obstruction to urinary flow
causes hydronephrosis in Infants and
children
- 20% bilateral UPJ present early
- Preferentially in males
- bilateral associated with other congenital
anomalies
urinary stasis within
diverticula→recurrent
infection
bladder calculi (from urinary stasis)
bladder
- Ascending Urinary Tract Infection
-
-
(result of vesicoureteral orifice →
vesicoureteral reflux)
Chronic reflux-associated
pyelonephritis (CRAP): common
cause of chronic pyelonephritis
-
- CRAP: results from
Pathogenesis
- most small and asymptomatic
superimposition of UTI on
congenital vesicoureteral reflux and - can be clinically significant: cause sites
intrarenal reflux
- kidney fail to develop
to normal size
- development of metanephros - fusion of upper (10%) or
-
into kidney occurs in ectopic
foci
lie either just above pelvic
brim or sometimes within
pelvis
Normal or slightly small in
size (otherwise unremarkable)
lower poles (90%) of kidneys
produce a horseshoe-shaped
that is continuous across the
midline anterior to great
vessels
- associated with distinct double renal
pelves or with anomalous
development of a large kidney having
a partially bifid pelvis terminating in
separate ureter
- May pursue separate course to
bladder but commonly join within
within bladder wall and drain through
area single ureteral orifice
- saccular outpouchings of
-
ureteral wall
Dilation (hydroureter),
elongation, tortuousity of
ureter
- Reflux and associated renal
damage: unilateral or bilateral
- congenital diverticula: due to focal
-
failure of development of normal
musculature OR some urinary tract
obstruction during fetal development
Can be acquired
pouchlike evaginations of bladder wall
< 1cm to 5 to 10 cm
Hypospadias
Hypospadias:
- more common
- 1 in 300 live male births
- Even when isolated, these urethral
defects have clinical significance bc
the abnormal opening is often
constricted resulting in urinary
tract obstruction and increased risk
of ascending UTI
- When orfices are near base of
penis, normal ejaculation and
insemination are hampered and may
cause sterility
- exposed bladder mucosa can
undergo colonic glandular
metaplasia
Urachal cysts →glandular
tumors or carcinomas
- minority of bladder cancers
(0.1-0.3%)
- 20-40% badder
adenocarcinoma
- associated with failure of normal
- development failure in anterior
- urachus patent in part of in
- malformation of urethral groove canal
creating abnormal urethral opening
either on ventral surface of the penis
(Hypospadias) or dorsal surface
(Epispadia)
insufficiency
Unilateral agenesis: in solitary
kidney
- enlarges and hypertrophy to
compensate
- Can develop glomerular sclerosis
due to adaptive changes in
hypertrophied nephrons→CKD
Urachal anomalies
upper levels dues to exposed
bladder
↑ risk for adenocarcinoma
arising in remnant bladder
Lesions may be surgically
corrected
Long term survival is possible
w. urinary stasis
- Bilateral → chronic renal
Structural
Morphology
Congenital Anomalies of the penis
-
wall abdomen and bladder
bladder communicates directly
thru a large defect with surface
of body or lies as an opened
sac
-
-
whole
Normally: urachus (canal
that connects the fetal
bladder with allantois) is
obliterated after birth
totally patent: fistulous
urinary tract connects
bladder with umbilicus
Others with only central
region of urachus persists
→urachal cysts lined by
descent of testes with
malformations of urinary tract
Cystic Diseases of Kidney
Cystic Diseases of Renal medulla
Inheritance
Pattern
Etiology
Autosomal Dominant (adult) Polycystic
kidney Disease
Automsonal Recessive (childhood)
Polycystic kidney Disease
- autosomal dominant with high penetrance
Nephronophtsis
Adult onset medullary cystic
disease
- Autosomal Recessive
-autosomal recessive traits
- autosomal dominant
- inheritance of one mutated copy of AKPD
- Genetically distinct from adult PKD
- Mutations in PKHD1 gene, which maps to
- familial forms: inherited as autosomal recessive - mutations in MCKD1 and MKCD2
-
-
-
-
Presentation
-
traits
- usually manifest in childhood or adolescence
- as a group, nephronophthisis complex is now
most common genetic cause of ESRD in
children and young adults
- sixteen responsible gene loci, NPHP1 to
NPHP11 , JBTS2, JBTS3, JBTS11 are mutated
in juvenile forms of nephronophthisis
- 3 variants
1- sporadic, nonfamilial
2- Familial Juvenile nephronophthisis (most
common)
3- Renal-retinal dysplasia (15 %) in which the
kidney disease is accompanied by ocular lesions
chromosome region 6p21-p23
Analysis of AR PKD have revealed a wide
range of different mutations
vast majority of cases are compound
heterozygotes, complicating molecular
diagnosis of disorder
- Large kidneys are palpable abdominally as
- Defined depending on time of presentation - condition in adults and usually
-
-
-
Organ Morphology
gene
mutation of other allele acquired in somatic
cells of kidney which causes faster disease
progression and increased disease severity
In 85-90% of families, PKD1 on short arm of
chrom 16 is the defective gene (encodes a
large (460-kDA) and complex cell membrane
associated protein called polycystin-1)
PKD2 gene : 10-15% pts; reside on chrom 4
and encodes polycystin-2 (smaller, 110 kDa
Protein)
1/400- 1000 live births
5-10% of cases of ESRD requiring
transplantation or dialysis
Mutation in either gene gives rise to same
phenotype; pts with PKD2 mutations have a
slower rate of disease progression
compared to patient with PKD1 mutations
Medullary sponge kidney
masses extending into pelvis
symptoms appears in 4th decade of life by
which time the kidneys are quite large
Common complaint: flank pain or heavy
dragging sensation
Excruciating pain from acute distention of
cyst, either by intracystic hemorrhage or by
obstruction
sometimes attention is first drawn to lesion
on palpation of an abdominal mass
intermittent gross hematuria is common
most important complications are
hypertension and urinary infection: HTN of
variable severity in 75% pts
saccular aneurysms of circle of willis:
10-30% pts; associated w high incidence of
Subarachnoid hemorrhage
asymptomatic liver cysts: 1/3rd pts
mitral valve prolapse & other cardiac valvular
anomalies in 20-25% pts; most
asymptomatic
- multiple expanding cysts of BOTH kidneys
-
—> destroy the renal parenchyma and
cause renal failure
kidney may reach enormous size (up to 4
kg/kidney)
-
-
& presence of associated hepatic lesions
perinatal, neonatal, infantile and juvenile
subcategories
Perinatal & neonatal: most common;
serious manifestations present @ birth &
young infant may die from hepatic and
renal failure
Pts who survive infancy develop liver
cirrhosis (congenital hepatic fibrosis)
-
discovered radiographically
Usually normal renal fx
pathogenesis is unknown
-
- multiple cystic dilations of
-
-
appearance
numerous small cysts in cortex and
medulla gives it spongelike appearance
-
collecting ducts in the medulla
papillary ducts in medulla are
dilated
small cysts maybe present
- Dilated elongated channels are present at
- kidney composed of solely cysts of up to 3
or 4 cm with NO intervening parenchyma
- cysts filled with fluid, which may be clear,
-
-
-
variable # of cysts in medulla, usually
concentrated at the corticomedullary junction
Small kidneys
contracted granular surfaces & cysts in
medulla: prominent @ corticomedullary
junction
agenesis or atresia and other abnormalities of Lower
urinary tract
- asymptomatic, may bleed→hematuria
- progressive renal disorders
characterized by variable # of cysts
in medulla, usually concentrated at
the corticomedullary junction
- enlarged, extremely irregular and multi-cystic
- cyst vary in size from several mm to cm
- numerous cysts in cortical & medullary
- cysts measure 0.1 to 4cm in diameter, contain
clear fluid
- finding almost always include multiple
epithelium lined liver cysts and
proliferation of portal bile ducts
- cysts: lined by cuboidal epithelium
-
or occasionally by transitional
epithelium
cortical scarring is absent unless
superimposed pyelonephritis
present
- Cysts are lined by flattened or cuboidal
- cysts lined by flattened by epithelium
- Cysts are lined by either hyperplastic or flattened
- presence of islands of undifferentiated mesenchyme,
tubular epithelium
epithelium and are usually surrounded by
inflammatory cells or fibrous tissue
often with cartilage and immature collecting ducts
- in cortex: widespread atrophy and thickening
- often contain calcium oxalate crystals due to
of tubular basement membranes, together
with interstitial fibrosis
Treatment/
Prognosis
-
Normal
disease is fatal
prognosis is favorable than with most CKD
progresses slowly
ESRD occurs by ~50 yrs but there is wide
variation, nearly normal lifespans reported
pts in whom disease progresses to renal
failure are treated by renal transplantation
Death from uremia or hypertensive
complication
- Polycystin 1 protein has a large extracellular
-
-
domain and multiple transmembrane regions
extracellular domains have regions that can
bind to extracellular matrix
Polycystin-1 localizes to the primary cilium
of tubular cells, giving rise to concept of
renal cystic diseases as a type of ciliopathy.
cilia are hair organelles that project into
lumina from apical surface of tubular cells,
where they serve as mechanosensors of
fluid flow
Polycystin 2 seems to function as a Capermeable membrane channel and is
localized to cilia
polycystin 1 and 2 are believed to work
together by forming heterodimers
- expected course is progression to ESRD in 5-10
years
obstruction of tubules by interstitial fibrosis or by
oxalate crystals
- progression to end stage kidney
disease in adult life
- unilateral: dysplasia mimic a neoplasm and lead to
surgical exploration and nephrectomy
- bilateral: renal failure may ultimate results
- End stage renal disease who have undergone
prolonged dialysis
- 12-18x ↑ risk for renal cell carcinoma in 7% of
dialyzed pts observed for 10 yrs
- gene is highly expressed in adult and fetal
-
-
kidney and also in liver and pancreas
PKHD1 gene encodes fibrocystin and
integral membrane protein with large
extracellular region, a single
transmembrane component, & short
cytoplasmic tail
Fibrocystin hs been localized to the
primary cilium of tubular cells
function of fibrocystin is unknown , but it
may be a cell surface receptor with a role
in collecting duct and biliary differentiation
- NPHP1 to NPHP11: encode Nephrocystins
proteins
- NPHP and JBTS proteins are present in
primary cilia, basal bodies attached to these
cilia or the centrosome organelle from which
basal bodies originate
single or multiple
Usually involves cortex
1 to 5-10cm or more in size
Translucent
Lined by smooth membrane
contours, almost always
avascular , fluid signals on
US
turbid or hemorrhagic
Cellular
Morphology
-
- Filled with clear fluid
- Radiologic findings: smooth
- small cysts may be seen in cortex
right angles to the cortical surface,
completely replacing medulla and cortex
Simple cysts
- associated with ureteropelvic obstruction, ureteral
polydipsia, reflects marked defect in
concentrating ability of renal tubules
some syndromic variants of nephronophthisis
can have extrarenal associations, including
ocular motor abnormalities, renal dystrophy,
liver fibrosis and cerebellar abnormalities
Diagnosis: few specific clues because
medullary cysts might be too small to be
visualized radiographically
Disease should be considered in children/
adolescents with otherwise unexplained
chronic renal failure, + family history, and
chronic tubulointerstitial nephritis on biopsy
- progressive renal disorder characterized by
Acquired (dialysis-associated) cystic Disease
- Acquired thru dialysis
- affected children present first with polyuria and
-
- kidneys enlarged with smooth external
cause medullary cystic disease
multicystic Renal Dysplasia