CAKUT + cystic disease Flashcards
(44 cards)
nephronophthisis:
- histology
- cysts - where?
- symptoms
tubulointerstitinal nephritis, tubular atrophy, glomerulosclerosis
cysts - esp in corticomedullary junction
polydipsia/polyuria
how do nephronophthisis and medullary cystic kidney disease differ?
MCKD in adulthood, and polyuria/polydypsia/gout only
how many renal cysts do we tolerate as normal variation?
1 renal cyst per year of life
PCKD (AD and AR)
- where are the cysts
- uni/bilateral kidneys
- common complications
cortical and medullary cysts
BILATeral
stones, RAAS > HTN, renal failure
ADPKD vs ARPKD
- age
- mutation
- cyst size
- cyst location
ADPKD:
- adult onset normally (unless PKD1 mutation, earlier, more severe )
- PKD1/2 mutation (polycystins) - two hit hypothesis
- cysts macro usually
- all parts of nephron
ARPKD:
- often renal failure before birth
- PKHD1 mutation (fibrocystin) - similar mechanism as ADPKD
- cysts micro
- collecting duct only
how do PKD1 and PKD2 mutations cause PCKD?
encode for primary cilium
in nephron, they allow Ca influx to inhibit cell proliferation
without the inhibiting signal, this allows water to enter > cysts
ADPKD - other abnormalities that are associated
liver cysts
pancreas cysts
hernias/diverticula
seminal vesicle cysts
aortic arch dilation
berry aneurysms
ARPKD - other associated abnormalities
oligohydramnios»_space; Potter sequence: clubbed feet, flat nose, pulmonary hypoplasia»_space; death
congenital liver fibrosis!!! > portal HTN > oesophgeal varices etc.
bile duct dilatation (Caroli’s disease) and cholestasis
MCDK vs PCKD
- inheritance
- uni/bilateral
- how the cysts form
MCDK:
sporadic, usually unilateral
ureteric bud malformation > urine backs up > cysts - it doesn’t function!
PCKD
AD(mostly)/AR, bilateral
cilia abnormal > cysts
most common hereditary human kidney disease is…
…ADPKD (1/400-1/1000)
nephronophthisis - what extra-renal manifestations can they have?
genes encoding cilia/centrosome, so can have other things wrong
some = skeletal: polydacytyly, craniosynotosis etc.
nephronophthisis = neuro = dev delay, hypotonia
children = cardiac: sinus invertus
have = hepatic: fibrosis
extra-renal = eye, retinitis pigmentosa
infantile nephronophthisis vs juvenile
infantile - onset before 3yo, severe HTN, extra-renal manifestations more common 80% - esp **situs invertus
juvenile - later onset, ESRF ~13yo, more common!
name the 4 syndromic cystic renal diseases to know, and what cystic disease are they associated with
Just bring me oreos:
joubert - NPHP
bardet-biedl - NPHP
meckel-gruber - NPHP
orofacial digital syndrome type 1 - ADPKD
Joubert syndrome - key clinical triad
i. Cerebellar and brainstem malformation = molar tooth sign (vermal aplasia)
ii. Hypotonia
iii. Developmental delays
(and renal disease - a/w NPHP)
pathogenesis of why tuberous sclerosis and renal disease are related, and what kind of renal disease is related
TSC2 lies adjacent to PKD1 –> contiguous deletions.
• 75% develop angiomyolipomata
• 20% develop simple cysts
• PCKD develops in <5%
• can also get RCC
how is diabetes associated with renal cystic disease?
MODY5 - mutation HNF1B (hepatocyte nuclear factor 1 B) –> T2DM + renal cysts, also a/w PKD1
MCKD now known as?
ADTKD = autosomal dominant tubulointerstitial kidney disease
summary of embryonic nephrogenesis
- week 4: intermediate mesoderm > urogenic ridge > nephrogenic cord > pronephros
- week 4-5: mesonphros: more tubules. fuse with cloaca. ureteral bud forms.
- week 5 metanephros begins: ureteral bud grows into the metanephric blastema to continually divide into collecting system. metanephric mesoderm form cap on the collecting tubules, and the tubules signal the mesoderm to make the…nephron.
when to do USS post birth?
- USS within 24 hours of life for any infants with bilateral involvement/ solitary affected kidney
- All other scans should be performed at D4-5: to ensure adequate renal plasma flow and rise in GFR
what other abnormalities are CAKUT associated with?
single umbilical artery, external ear anomalies, imperforate anus and scoliosis
renal agenesis vs aplasia
agenesis = no tissue
aplasia = nubbin of tissue
conditions associated with renal agenesis / aplasia
- single umbilical artery
- contralateral VUR
- mullerian defects
- branchio-oto-renal syndrome
- syndromes - VATER, turner
name 5 causes of the potter sequence
MARCO:
medullary hypoplasia
AR PCKD (infantile)
renal hypoplasia
cystic renal dysplasia
obstructive uropathy
MCDK associated with what contralateral disease
1/3 have abnormal contralateral kidney:
VUR
obstruction/ ectopic ureter
hydronephrosis
