Congenital Anomalies of Kidney and Lowe Urinary Tract

Congenital Anomalies of kidney Congenital Anomalies of Ureters Congenital Anomalies of the Bladder Congenital Anomalies of the penis

Agenesis of Kidney Hypoplasia Ectopic Kidneys Horseshoes kidneys Double & Bifid Ureters Ureteropelvic Junction obstruction Diverticula Vesicuretral reflux Diverticula of the bladder Exstrophy of Bladder Urachal anomalies Hypospadias

Clinical Bilateral:
- Bilateral→renal failure - Predisposes it to bacterial - 1 in 500 to 1000 autopsies
- most unilateral; no clinical significance - congenital disorder that commonly - uncommon lesions
- most common
- Predispose infection and formation of - risk for infections that spread to - carcinoma
Hypospadias:

Presentation - incompatible with life

in childhood
infection bc of abnormal causes hydronephrosis in Infants and - Congenital or acquired
- Serious congenital anomaly of bladder calculi (from urinary stasis) upper levels dues to exposed - more common

- encountered in stillborn infants

- Unilateral common
position, kinking or tortuosity children
- Most asymptomatic but bladder
bladder
- 1 in 300 live male births

- associated w. limb defect and - True renal hypoplasia of ureters that causes - 20% bilateral UPJ present early
urinary stasis within - Ascending Urinary Tract Infection - ↑ risk for adenocarcinoma - Even when isolated, these urethral
Hypoplastic lungs
observed in Low Birth obstruction to urinary flow
- Preferentially in males
diverticula→recurrent (result of vesicoureteral orifice → arising in remnant bladder
defects have clinical significance bc
infants
- bilateral associated with other congenital infection vesicoureteral reflux)
- Lesions may be surgically the abnormal opening is often
Unilateral agenesis:
- Increased lifetime risk anomalies - Chronic reflux-associated corrected
constricted resulting in urinary
- uncommon
for CKD pyelonephritis (CRAP): common - Long term survival is possible tract obstruction and increased risk
- Unilateral: compatible with life if cause of chronic pyelonephritis of ascending UTI

no other abnormalities exist - When orfices are near base of

penis, normal ejaculation and
insemination are hampered and may
cause sterility

Pathogenesis
undergo colonic glandular
descent of testes with
- CRAP: results from - exposed bladder mucosa can Urachal cysts →glandular - associated with failure of normal
superimposition of UTI on - most small and asymptomatic
tumors or carcinomas
congenital vesicoureteral reflux and - can be clinically significant: cause sites metaplasia - minority of bladder cancers malformations of urinary tract

intrarenal reflux
w. urinary stasis
(0.1-0.3%)

- Bilateral → chronic renal - 20-40% badder

insufficiency adenocarcinoma

Structural Unilateral agenesis: in solitary - kidney fail to develop - development of metanephros - fusion of upper (10%) or - associated with distinct double renal - saccular outpouchings of - Reflux and associated renal - congenital diverticula: due to focal - development failure in anterior - urachus patent in part of in - malformation of urethral groove canal
Morphology kidney
to normal size into kidney occurs in ectopic lower poles (90%) of kidneys pelves or with anomalous ureteral wall
damage: unilateral or bilateral failure of development of normal wall abdomen and bladder
whole
creating abnormal urethral opening
- enlarges and hypertrophy to foci
produce a horseshoe-shaped development of a large kidney having - Dilation (hydroureter), musculature OR some urinary tract - bladder communicates directly - Normally: urachus (canal either on ventral surface of the penis
compensate
- lie either just above pelvic that is continuous across the a partially bifid pelvis terminating in elongation, tortuousity of obstruction during fetal development
thru a large defect with surface that connects the fetal (Hypospadias) or dorsal surface
- Can develop glomerular sclerosis brim or sometimes within midline anterior to great separate ureter
ureter - Can be acquired
of body or lies as an opened bladder with allantois) is (Epispadia)
due to adaptive changes in pelvis
vessels - pouchlike evaginations of bladder wall
sac
obliterated after birth

hypertrophied nephrons→CKD
- Normal or slightly small in - May pursue separate course to - < 1cm to 5 to 10 cm
- totally patent: fistulous
size (otherwise unremarkable) bladder but commonly join within urinary tract connects
within bladder wall and drain through bladder with umbilicus

area single ureteral orifice - Others with only central

region of urachus persists
→urachal cysts lined by
 Cystic Diseases of Kidney
Cystic Diseases of Renal medulla

Autosomal Dominant (adult) Polycystic Automsonal Recessive (childhood) Medullary sponge kidney Nephronophtsis Adult onset medullary cystic multicystic Renal Dysplasia Acquired (dialysis-associated) cystic Disease Simple cysts
kidney Disease Polycystic kidney Disease disease

Inheritance - autosomal dominant with high penetrance - Autosomal Recessive -autosomal recessive traits - autosomal dominant - Acquired thru dialysis
Pattern

Etiology - Genetically distinct from adult PKD

- familial forms: inherited as autosomal recessive - mutations in MCKD1 and MKCD2 - associated with ureteropelvic obstruction, ureteral
- inheritance of one mutated copy of AKPD - Mutations in PKHD1 gene, which maps to traits
cause medullary cystic disease agenesis or atresia and other abnormalities of Lower
gene
chromosome region 6p21-p23
- usually manifest in childhood or adolescence
urinary tract
- mutation of other allele acquired in somatic - Analysis of AR PKD have revealed a wide - as a group, nephronophthisis complex is now
cells of kidney which causes faster disease range of different mutations
most common genetic cause of ESRD in
progression and increased disease severity
- vast majority of cases are compound children and young adults

- In 85-90% of families, PKD1 on short arm of heterozygotes, complicating molecular - sixteen responsible gene loci, NPHP1 to
chrom 16 is the defective gene (encodes a diagnosis of disorder
NPHP11 , JBTS2, JBTS3, JBTS11 are mutated
large (460-kDA) and complex cell membrane - in juvenile forms of nephronophthisis

associated protein called polycystin-1)

- 3 variants

- PKD2 gene : 10-15% pts; reside on chrom 4 1- sporadic, nonfamilial

and encodes polycystin-2 (smaller, 110 kDa 2- Familial Juvenile nephronophthisis (most
Protein)
common)

- 1/400- 1000 live births

3- Renal-retinal dysplasia (15 %) in which the
- 5-10% of cases of ESRD requiring kidney disease is accompanied by ocular lesions
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

Presentation - Large kidneys are palpable abdominally as - Defined depending on time of presentation - condition in adults and usually - affected children present first with polyuria and - asymptomatic, may bleed→hematuria

masses extending into pelvis

& presence of associated hepatic lesions
discovered radiographically
polydipsia, reflects marked defect in
- symptoms appears in 4th decade of life by - perinatal, neonatal, infantile and juvenile - Usually normal renal fx
concentrating ability of renal tubules

which time the kidneys are quite large

subcategories
- pathogenesis is unknown - some syndromic variants of nephronophthisis
- Common complaint: flank pain or heavy - Perinatal & neonatal: most common; can have extrarenal associations, including
dragging sensation
serious manifestations present @ birth & ocular motor abnormalities, renal dystrophy,
- Excruciating pain from acute distention of young infant may die from hepatic and liver fibrosis and cerebellar abnormalities

cyst, either by intracystic hemorrhage or by renal failure

- Diagnosis: few specific clues because
obstruction
- Pts who survive infancy develop liver medullary cysts might be too small to be
- sometimes attention is first drawn to lesion cirrhosis (congenital hepatic fibrosis) visualized radiographically

on palpation of an abdominal mass

- Disease should be considered in children/
- intermittent gross hematuria is common
adolescents with otherwise unexplained
- most important complications are chronic renal failure, + family history, and
hypertension and urinary infection: HTN of chronic tubulointerstitial nephritis on biopsy
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

Organ Morphology - multiple expanding cysts of BOTH kidneys - kidneys enlarged with smooth external - multiple cystic dilations of - progressive renal disorder characterized by - progressive renal disorders - enlarged, extremely irregular and multi-cystic
- numerous cysts in cortical & medullary
- single or multiple

—> destroy the renal parenchyma and appearance

collecting ducts in the medulla
variable # of cysts in medulla, usually characterized by variable # of cysts - cyst vary in size from several mm to cm
- cysts measure 0.1 to 4cm in diameter, contain - Usually involves cortex

cause renal failure

- numerous small cysts in cortex and - papillary ducts in medulla are concentrated at the corticomedullary junction in medulla, usually concentrated at clear fluid - 1 to 5-10cm or more in size

- kidney may reach enormous size (up to 4 medulla gives it spongelike appearance
dilated
- Small kidneys
the corticomedullary junction
- Translucent

kg/kidney)
- small cysts maybe present
- contracted granular surfaces & cysts in - Lined by smooth membrane

medulla: prominent @ corticomedullary

junction

- Filled with clear fluid

- Dilated elongated channels are present at - Radiologic findings: smooth

right angles to the cortical surface, - small cysts may be seen in cortex
contours, almost always
- kidney composed of solely cysts of up to 3 completely replacing medulla and cortex
avascular , fluid signals on
or 4 cm with NO intervening parenchyma
- US
- cysts filled with fluid, which may be clear,
turbid or hemorrhagic

Cellular - finding almost always include multiple - cysts: lined by cuboidal epithelium - Cysts are lined by flattened or cuboidal - cysts lined by flattened by epithelium
- Cysts are lined by either hyperplastic or flattened
Morphology epithelium lined liver cysts and or occasionally by transitional epithelium and are usually surrounded by - presence of islands of undifferentiated mesenchyme, tubular epithelium

proliferation of portal bile ducts epithelium

inflammatory cells or fibrous tissue
often with cartilage and immature collecting ducts
- cortical scarring is absent unless
superimposed pyelonephritis
present

- in cortex: widespread atrophy and thickening - often contain calcium oxalate crystals due to
of tubular basement membranes, together obstruction of tubules by interstitial fibrosis or by
with interstitial fibrosis
oxalate crystals
Treatment/ - disease is fatal
- expected course is progression to ESRD in 5-10 - progression to end stage kidney - unilateral: dysplasia mimic a neoplasm and lead to - End stage renal disease who have undergone
Prognosis - prognosis is favorable than with most CKD
years disease in adult life surgical exploration and nephrectomy
prolonged dialysis

- progresses slowly
- bilateral: renal failure may ultimate results - 12-18x ↑ risk for renal cell carcinoma in 7% of
- ESRD occurs by ~50 yrs but there is wide dialyzed pts observed for 10 yrs
variation, nearly normal lifespans reported

- pts in whom disease progresses to renal

failure are treated by renal transplantation

- Death from uremia or hypertensive

complication

Normal - Polycystin 1 protein has a large extracellular - gene is highly expressed in adult and fetal - NPHP1 to NPHP11: encode Nephrocystins
domain and multiple transmembrane regions
kidney and also in liver and pancreas
proteins

- extracellular domains have regions that can
bind to extracellular matrix
integral membrane protein with large
- Polycystin-1 localizes to the primary cilium
of tubular cells, giving rise to concept of
renal cystic diseases as a type of ciliopathy.
- PKHD1 gene encodes fibrocystin and - NPHP and JBTS proteins are present in
primary cilia, basal bodies attached to these
extracellular region, a single cilia or the centrosome organelle from which
transmembrane component, & short basal bodies originate
cytoplasmic tail

cilia are hair organelles that project into - Fibrocystin hs been localized to the
lumina from apical surface of tubular cells, primary cilium of tubular cells

where they serve as mechanosensors of - function of fibrocystin is unknown , but it

fluid flow
may be a cell surface receptor with a role
- Polycystin 2 seems to function as a Ca- in collecting duct and biliary differentiation

permeable membrane channel and is

localized to cilia

- polycystin 1 and 2 are believed to work

together by forming heterodimers