Cystic Disease

Question 1

What are the 2 causative genes of autosomal dominant polycystic kidney disease?

Answer 1

PKD1 and PKD2

Question 2

Which ADPKD mutation has a worse prognosis?

Answer 2

PKD1 mutations

Question 3

What is the 2nd-hit hypothesis of ADPKD?

Answer 3

The theory that cyst formation does not occur until there is a 2nd hit/mutation that occurs in the unaffected gene copy

Question 4

What cellular structure do PKD1 and PKD2 localize to?

Answer 4

Cilium of tubular epithelial cells

Question 5

What is the affect of abnormal cilliary function on Ca2+ and cAMP?

Answer 5

It decreases intracellular Ca2+ and raises cAMP levels, which leads to cell proliferation and fluid secretion of expanding cyst

Question 6

What is the role of ADH on cyst formation?

Answer 6

Binding of ADH/AVP to V2 receptors stimulates cAMP, which leads to cyst proliferation and fluid secretion into cysts

Question 7

How does ADPKD lead to CKD/ESRD?

Answer 7

Cysts take up more and more of the kidney space, which leads to compression of renal vasculature and RAAS activation. There is also functional tissue destruction, which leads to hyperfiltration and injury of remaining kidney units

Question 8

What is the mainstay of diagnosis of cystic kidney disease?

Answer 8

Imaging and family history if possible

Question 9

What are common renal manifestations of ADPKD?

Answer 9

Hypertension, abdominal/flank pain, proteinuria, nephrolithiasis, hematuria, UTIs

Question 10

What are extrarenal complications of ADPKD?

Answer 10

Hepatic cysts (most common)
Intracranial aneurysms (can be fatal)
Mitral valve prolapse, aortic aneurysm

Question 11

What is the treatment for ADKPD?

Answer 11

General renoprotection (BP control, low sodium diet, increased water intake, minimal caffeine, no contact sports) and newer pharmacology (tolvaptan, mTOR inhibitors)

Question 12

What is the gene associated with autosomal recessive PKD?

Answer 12

PKHD1 gene that encodes for fibrocystin (expressed in primary cilia of kidney and bile duct epithelia)

Question 13

What is the pathology of ARPKD?

Answer 13

Enlarged, echogenic kidneys, compressed cortex, dilated branching collecting ducts

Question 14

How is ARPKD diagnosed?

Answer 14

Presence of large, echogenic kidneys with either concurrent hepatic fibrosis, parents without cystic kidneys, or sibling with disease)

Question 15

What are extra-renal clinical manifestations of ARPKD?

Answer 15

Billiary dysgenesis, hepatic fibrosis, portal hypertension

Question 16

What is medullary cystic kidney disease?

Answer 16

A group of autosomal dominant disorders characterized by minimal urinary abnormalities and histologic evidence of tubular and interstitial fibrosis

Question 17

What two conditions is medullary cystic kidney disease associated with?

Answer 17

Hyperuricemia and gout

Question 18

What are the genetic mutations associated with medullary cystic kidney disease?

Answer 18

MUC1 gene and UMOD

MUC1 - mucin gene
UMOD - role in vesicle trafficking on the thick ascending limb, may also limit water permeability

Question 19

What are the extra-renal manifestations of medullary cystic kidney disease?

Answer 19

None

Question 20

What is the pathogenesis of ADPKD?

Answer 20

Abnormal function of cilia on tubular epithelial cells, which leads to dysregulation of intracellular signaling that results in cell proliferation and fluid secretion into cysts