Genetic Cystic Kidney Dz Flashcards
What genetic abnormalities is ADPKD associated with?
berry aneurysms (15%), hepatic cysts (40%), mitral valve prolapse (25%)
What is the most common form of renal cystic disease?
autosomal dominant polycystic kidney disease - incidence is 1 in 700
Patients with ADPKD progress to renal failure in which decades of life?
30s to 50s
Which form of PKD is invariably fatal?
autosomal recessive
Which form of PKD is deadly in 30% of births?
autosomal recessive
Which form of PKD leads to ESRD by ten years of life?
autosomal recessive
What is a common presentation of ADPKD in teens?
hematuria following injury to the flank region
What are some common complications of ADPKD?
cyst rupture, pain, and recurrent UTIs
Which genes are mutated in ADPKD?
PKD1 and PKD2
a minority of patients have a PKD3 mutation
What is the most common gene mutated in ADPKD?
PKD 1, on chromosome 16
What is the pathogenesis of ADPKD?
cell-to-cell or cell matric interactions cause cell proliferation and fluid formation, which causes cysts to form in interstitial and tubular areas
Which form of PKD involves all of the collecting ducts bilaterally and frequently presents with hepatic fibrosis, portal hypertension, and splenomegaly?
ARPKD
Which form of PKD presents as longitudinal cysts oriented at right angles to the cortical surface?
ARPKD
What conditions can lead to acquired PKD?
ESRD with hemodialysis for 2+ years
What is thought to be the causative factor in acquired PKD?
Azotemia, due to the fact that the problem reverses after renal transplant
What form of PKD is associated with renal adenomas and renal cell carcinoma?
acquired PKD after consistent hemodialysis due to ESRD
What form of cystic kidney disease is associated with “spongey” cysts in the collecting ducts, hematuria, recurrent infections, and urinary calculi?
medullary sponge disease
which type of cystic kidney disease is a ‘fake’ disease, per Dr. Cheema/
medullary sponge disease - it’s frequently an incidental finding that has no effect on kidney function, no risk for CKD or ESRD, but may increase risk for kidney stones
What form of cystic disease affects the cortico-medullary junction, leading to salt wasting, polyuria, and progressive renal failure?
medullary cystic disease
not to be confused with medullary SPONGE disease
What is the most common monogenic cause of ESRD wordwide, and the 4th leading cause of ESRD in the US?
ADPKD
What is the somatic second hit hypothesis in ADPKD?
The idea that since not all nephrons show cyst formation in ADPKD, the disease requires some kind of somatic second hit for epithelial dysfunction to present, making it an AR disease at the tissue level
What intracellular substances are affected in ADPKD, which eventually lead to cyst formation?
Deficiency in the epithelial genes leads to decreased Ca and increased cAMP
What role does ADH have in ADPKD?
it is thought to increase cyst formation, which increases the tubular obstruction
Why is the 3D volume of kidneys an important parameter to be measured in ADPKD?
it predicts rate of cyst formation and the drop in GFR over time, which gives you an idea of how aggressive management needs to be
What factors are used in diagnosing ADPKD?
family history, ultrasound, matching expected number of cysts to age
** genetic testing is rarely used
What are some of the renal signs of ADPKD?
hypertension flank pain proteinuria nephrolithiasis hematuria UTI/pyelo
What is a special consideration of managing ADPKD in women?
estrogen - it can increase the risk of hepatic cyst formation
What are the mainstays of treatment for ADPKD?
BP control (aggressive) low sodium and caffeine intake avoid contact sports water intake of 3L daily (minimize ADH secretion)
What is a novel therapy that just got approved for ADPKD?
V2 receptor antagonists (tolvaptan) – prevents ADH signalling, which reduces cyst formation
currently only used for pts with “high risk of progression”
Oligohydramnios, pulmonary hypoplasia, limb defects, and enlarged cystic kidneys are signs of what congenital defect?
ARPKD
What conditions can cause biliary dysgenesis, hepatic fibrosis, portal hypertension, and cholangitis?
ARPKD
What genetic cystic disease presents with small cysts in only 50% of patients and is frequently associated with hyperuricemia and gout?
medullary cystic kidney disease
What cystic disease has no extrarenal manifestations?
medullary cystic kidney disease
What is prevalence of ADPKD in general population?
the incidence is 1 in 700, so around there
Which form of polycystic disease is associated with cerebral aneurysms?
ADPKD
What are the 3 postulated mechanisms that are responsible for the formation of a cyst in ADPKD patients?
- low IC calcium and high cAMP
- ADH signalling
- somatic second hit
Is the glomerular involvement in a given cystic disease a common occurrence?
NO?
** check answer
Which form of PKD is associated with hepatic fibrosis?
ARPKD
