SM_215a: Genetic Cystic Kidney Disease

Question 1

_____ is the most common monogenic cause of ESRD worldwide

Answer 1

ADPKD is the most common monogenic cause of ESRD worldwide

Question 2

ADPKD is due to mutations in _____ and _____, which are functional components of ______

Answer 2

ADPKD is due to mutations in PKD 1 and PKD 2, which are functional components of tubular epithelial cells

Question 3

PKD1 accounts for _____ cases of ADPKD and is _____ severe

Answer 3

PKD1 accounts for most cases of ADPKD and is more severe

Question 4

Inheritance of ADPKD is ______

Answer 4

Inheritance of ADPKD is autosomal dominant

(5% due to de novo mutations)

Question 5

ADPKD exhibits _____ phenotypic variability

Answer 5

ADPKD exhibits significant phenotypic variability

(many mutations in each gene, severity of illness affected by specific mutation, somatic second-hit mutation)

Question 6

ADPKD is a _____pathy

Answer 6

ADPKD is a ciliopathy

Question 7

In ADPKD, cAMP _____ and Ca _____, leading to formation of _____

Answer 7

In ADPKD, cAMP increases and Ca decreases, leading to formation of cysts

Question 8

In ADPKD, increased ADH causes cysts to grow _____

Answer 8

In ADPKD, increased ADH causes cysts to grow faster

Question 9

In ADPKD, normal kidney tissue is replaced with large cysts, causing _____ and _____

Answer 9

In ADPKD, normal kidney tissue is replaced with large cysts, causing tubular obstruction and RAAS activation

Question 10

ADPKD causes _____ cysts and _____ enlarged kidneys

Answer 10

ADPKD causes innumerable cysts and bilaterally enlarged kidneys

(cysts variable in size, cysts push normal tissue out of the way)

Question 11

On histology, ADPKD manifests as _____

Answer 11

On histology, ADPKD manifests as very little normal kidney tissue between cysts

Question 12

In ADPKD, as total kidney volume increases, eGFR _____

Answer 12

In ADPKD, as total kidney volume increases, eGFR decreases

(total kidney volume is a good prognostic factor to predict rate of decline of GFR, a biomarker for ADPKD)

Question 13

Main extrarenal manifestations of ADPKD are ______ and ______

Answer 13

Main extrarenal manifestations of ADPKD are hepatic cysts and intracranial aneurysms

Question 14

ARPKD has a _____ severe phenotype than ADPKD

Answer 14

ARPKD has a more severe phenotype than ADPKD

Question 15

Abnormalities of ARPKD are present in _____ or at _____

Answer 15

Abnormalities of ARPKD are present in utero or at birth

(fetal abnormalities are oligohydramnios, pulmonary hypoplasia, and limb defects)

Question 16

ARPKD is causes by a genetic mutation in _____, which encodes _____

Answer 16

ARPKD is causes by a genetic mutation in PKHD1 gene, which encodes for fibrocystin

(fibrocystin found in primary cilia of tubular epithelial cells and bile duct epithelial cells)

Question 17

ARKPD most commonly affects _____, and abnormalities in _____ and _____ occur together

Answer 17

ARKPD most commonly affects children, and abnormalities in kidney and liver occur together

Question 18

In ARPKD, kidneys become large but _____

Answer 18

In ARPKD, kidneys become large but stabilize in size at some point

(in contrast to ADPKD)

Question 19

In ARPKD, cysts are _____

Answer 19

In ARPKD, cysts are longitudinal

Question 20

Extrarenal ARPKD is always associated with _____ and _____, often leading to _____

Answer 20

Extrarenal ARPKD is always associated with biliary dysgenesis and congenital hepatic fibrosis, often leading to portal hypertension

(at risk for cholangitis)

Question 21

Medullary cystic kidney disease is characterized by histologic evidence of _____

Answer 21

MCKD is characterized by histologic evidence of tubular and interstitial fibrosis

Question 22

MCKD is associated with _____ urinary abnormalities

Answer 22

MCKD is associated with minimal urinary abnormalities (little proteinuria or hematuria)

(only 50% of patients have cysts)

Question 23

MCKD is associated with mutations in _____, _____, and _____

Answer 23

MCKD is associated with mutations in MUC1 (encodes mucin 1), UMOD (encodes uromodulin), and REN (encoded renin)

Question 24

MCKD is commonly associated with _____ and _____

Answer 24

MCKD is commonly associated with hyperuricemia and gout (kidney stones)

Question 25

MCKD involves _____ CKD and _____ extrarenal manifestations

Answer 25

MCKD involves progressive CKD and no extrarenal manifestations

Question 26

Medullary sponge kidney involves ______, ______, and normal ______

Answer 26

Medullary sponge kidney involves small cysts in medulla that spare the cortex, nephrocalcinosis and nephrolithiasis, and normal renal function