Genetic Cystic Kidney Dz

Question 1

What genetic abnormalities is ADPKD associated with?

Answer 1

berry aneurysms (15%), hepatic cysts (40%), mitral valve prolapse (25%)

Question 2

What is the most common form of renal cystic disease?

Answer 2

autosomal dominant polycystic kidney disease - incidence is 1 in 700

Question 3

Patients with ADPKD progress to renal failure in which decades of life?

Answer 3

30s to 50s

Question 4

Which form of PKD is invariably fatal?

Answer 4

autosomal recessive

Question 5

Which form of PKD is deadly in 30% of births?

Answer 5

autosomal recessive

Question 6

Which form of PKD leads to ESRD by ten years of life?

Answer 6

autosomal recessive

Question 7

What is a common presentation of ADPKD in teens?

Answer 7

hematuria following injury to the flank region

Question 8

What are some common complications of ADPKD?

Answer 8

cyst rupture, pain, and recurrent UTIs

Question 9

Which genes are mutated in ADPKD?

Answer 9

PKD1 and PKD2

a minority of patients have a PKD3 mutation

Question 10

What is the most common gene mutated in ADPKD?

Answer 10

PKD 1, on chromosome 16

Question 11

What is the pathogenesis of ADPKD?

Answer 11

cell-to-cell or cell matric interactions cause cell proliferation and fluid formation, which causes cysts to form in interstitial and tubular areas

Question 12

Which form of PKD involves all of the collecting ducts bilaterally and frequently presents with hepatic fibrosis, portal hypertension, and splenomegaly?

Answer 12

ARPKD

Question 13

Which form of PKD presents as longitudinal cysts oriented at right angles to the cortical surface?

Answer 13

ARPKD

Question 14

What conditions can lead to acquired PKD?

Answer 14

ESRD with hemodialysis for 2+ years

Question 15

What is thought to be the causative factor in acquired PKD?

Answer 15

Azotemia, due to the fact that the problem reverses after renal transplant

Question 16

What form of PKD is associated with renal adenomas and renal cell carcinoma?

Answer 16

acquired PKD after consistent hemodialysis due to ESRD

Question 17

What form of cystic kidney disease is associated with “spongey” cysts in the collecting ducts, hematuria, recurrent infections, and urinary calculi?

Answer 17

medullary sponge disease

Question 18

which type of cystic kidney disease is a ‘fake’ disease, per Dr. Cheema/

Answer 18

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

Question 19

What form of cystic disease affects the cortico-medullary junction, leading to salt wasting, polyuria, and progressive renal failure?

Answer 19

medullary cystic disease

not to be confused with medullary SPONGE disease

Question 20

What is the most common monogenic cause of ESRD wordwide, and the 4th leading cause of ESRD in the US?

Answer 20

ADPKD

Question 21

What is the somatic second hit hypothesis in ADPKD?

Answer 21

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

Question 22

What intracellular substances are affected in ADPKD, which eventually lead to cyst formation?

Answer 22

Deficiency in the epithelial genes leads to decreased Ca and increased cAMP

Question 23

What role does ADH have in ADPKD?

Answer 23

it is thought to increase cyst formation, which increases the tubular obstruction

Question 24

Why is the 3D volume of kidneys an important parameter to be measured in ADPKD?

Answer 24

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

Question 25

What factors are used in diagnosing ADPKD?

Answer 25

family history, ultrasound, matching expected number of cysts to age

** genetic testing is rarely used

Question 26

What are some of the renal signs of ADPKD?

Answer 26

hypertension 
flank pain 
proteinuria
nephrolithiasis 
hematuria 
UTI/pyelo

Question 27

What is a special consideration of managing ADPKD in women?

Answer 27

estrogen - it can increase the risk of hepatic cyst formation

Question 28

What are the mainstays of treatment for ADPKD?

Answer 28

BP control (aggressive) 
low sodium and caffeine intake 
avoid contact sports 
water intake of 3L daily (minimize ADH secretion)

Question 29

What is a novel therapy that just got approved for ADPKD?

Answer 29

V2 receptor antagonists (tolvaptan) – prevents ADH signalling, which reduces cyst formation

currently only used for pts with “high risk of progression”

Question 30

Oligohydramnios, pulmonary hypoplasia, limb defects, and enlarged cystic kidneys are signs of what congenital defect?

Answer 30

ARPKD

Question 31

What conditions can cause biliary dysgenesis, hepatic fibrosis, portal hypertension, and cholangitis?

Answer 31

ARPKD

Question 32

What genetic cystic disease presents with small cysts in only 50% of patients and is frequently associated with hyperuricemia and gout?

Answer 32

medullary cystic kidney disease

Question 33

What cystic disease has no extrarenal manifestations?

Answer 33

medullary cystic kidney disease

Question 34

What is prevalence of ADPKD in general population?

Answer 34

the incidence is 1 in 700, so around there

Question 35

Which form of polycystic disease is associated with cerebral aneurysms?

Answer 35

ADPKD

Question 36

What are the 3 postulated mechanisms that are responsible for the formation of a cyst in ADPKD patients?

Answer 36

1. low IC calcium and high cAMP
2. ADH signalling
3. somatic second hit

Question 37

Is the glomerular involvement in a given cystic disease a common occurrence?

Answer 37

NO?

** check answer

Question 38

Which form of PKD is associated with hepatic fibrosis?

Answer 38

ARPKD