Polycystic Kidney Disease and other Ciliopathies Flashcards
What is CAKUT?
Congenital Anomalies of the Kidneys and Urinary Tract
How do kidneys work?
What do kidneys do?
- Regulate hormones that control blood
pressure, red blood cell production, and
calcium uptake - Maintain appropriate body fluid levels
- Control the amount of salt, water and other
electrolytes moving around the body
What are some signs of kidney disease?
- Anomalies on renal ultrasound
- Glomerular filtration rate (GFR)
– Estimate of how well your kidneys are filtering
waste from your blood - Protein in urine (proteinuria)
- Blood in urine (hematuria – can be
microscopic) - High blood pressure
- Electrolyte abnormalities
Congenital Anomalies of the Kidney
and Urinary Tract (CAKUT)
incidence
Fairly common
– 3 to 7 out of 1,000
livebirths
– 20% of congenital
anomalies
What are multicystic dysplastic kidneys?
What are the most common single gene causes of CAKUT (Congenital Anomalies of the Kidney
and Urinary Tract)?
-
PAX2 and HNF1B are most common single gene causes
– PAX2: papillorenal syndrome - Retinal coloboma
– HNF1B: renal cysts and diabetes syndrome - Early onset diabetes (before age 25)
- Deletions of this gene are common
- Can also have genital tract malformations
Non-motile cilia are very important developmentally. T or F?
True
Motile Cilia vs. Non-motile Cilia
Motile Cilia
* Found in the airway, brain
ventricles, fallopian tube,
and sperm
* They move (rhythmic
waving or beating back and
forth)
* Clear airway of mucus and
dirt
* Propel sperm and egg
* Determine left-right
organization of organs
during development
Non-motile Cilia
* Aka primary cilia
* Found on almost all human
cells
* Role is primarily sensory
* Coordinate cell signaling
pathways
* In kidney, bend with urine
flow
* In eye, found in
photoreceptors and allow
transport of molecules
across these cells
‘microscopic train-tracks’
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Genetics, Features, & Management
- PKD1 (85%)
- PKD2 (15%)
- adult onset usually
- bilaternal renal cysts that grow in number and size over time
- ~50% progress to end stage renal disease by 60
- Renal ultrasound: can diagnosis clinically
- If family hx of brain aneuyrsms brain MRI q 10 yrs
- Echo (if family history of aortic dilation/dissection or other cardiac involvement)
- Tolvaptan can slow decline of renal function
- dialysis or kidney transplant for those with ESRD
-** check donors for ADPKD b/c they should not be donating a kidney **
Occassionally ADPKD has digenic inheritence (pathogenic variants on 2 different genes), what does this cause?
more severe disease and/or earlier onset
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
- Most present in the neonatal period
- May be suspected on prenatal ultrasound
– Oligohydramnios with enlarged echogenic kidneys
– Impacts lung development
– 20-30% die within the neonatal period or first year of life due to respiratory insufficiency - More than 50% progress to ESRD within the first two decades
- Congenital hepatic fibrosis – contributing more to morbidity and mortality as treatment of renal and lung disease has improved
- Clinical variability: some may not present until adolescence or adulthood
- Incidence: 1 in 25,000 (less common)
- PKHD1 (most common)
- DZIP1L (more recently described)
more severe than ADPKD
Nephronophthisis
- Characterized by polyuria (frequent urination) and polydipsia
(increased thirst) due to reduced urine-concentrating ability - Chronic anemia and growth restriction
- Progression to ESRD typically before age 30
- Juvenile-onset is most common (median age of ESRD is 13 years)
- RUS findings include small to normal sized kidneys, increased
echogenicity, renal cyst formation - 80-90% of cases are isolated, 10-20% have extra-renal
manifestations - Autosomal recessive inheritance
- NPHP1 is the most common cause of isolated renal disease (about
85%)
– Whole gene deletions are very common
– NPHP1 is flanked by two large inverted repeats
Joubert Syndrome
molar tooth sign
Ciliopathy
