Cystic Diseases of the Kidney

Question 1

What is autosomal dominant polycystic kidney disease (ADPKD)?

Answer 1

• Hereditary disorder characterized by multiple expanding cysts that ultimately destroy the renal parenchyma anc cause renal failure

Question 2

Who is most likely affected by ADPKD?

Answer 2

• Adults

- Renal function is fine until the fourth or fifth decade

Question 3

How do individuals genetically acquire ADPKD?

Answer 3

• Must receive one copy of the mutated gene APKD and a mutation of the other allele is acquired in the somatic cells of the kidney

Question 4

What does the PKD1 gene encode for?

Answer 4

• A large integral membrane protein named polycystin-1 (which is expressed in tubular epithelial cells, particularly those of the distal nephron)

Question 5

What happens if PKD1 is mutated?

Answer 5

• It accounts for 85% of the cases of ADPKD

Question 6

What does the PKD2 gene encode for?

Answer 6

• Polycystin-2 which is an integral membrane protein that is expressed in all segments of the renal tubules and in many extrarenal tissues

Question 7

What does polycystin-2 do?

Answer 7

• Functions as a Ca2+ permeable cation channel

Question 8

What do polycystin-1 and polycystin-2 do together?

Answer 8

• Form a protein complex that regulates intracellular Ca2+ in response to fluid flow, perhaps because fluid moving through the kidney tubules causes ciliary bending that opens Ca2+ channels

Question 9

What does increased calcium do due to mutated PKD1 and PKD2 genes?

Answer 9

• Stimulate proliferation and secretion from epithelial cells lining the cysts, which together result in progressive cyst formation and enlargement

Question 10

What is the clinical presentation of ADPKD?

Answer 10

• Enlarged kidneys may induce a dragging sensation
• Occasionally begins with insidious onset of hematuria
• Proteinuria (usually less than 2g/day), polyuria, and HTN usually follow

Question 11

What causes the pain felt in ADPKD?

Answer 11

• Hemorrhagic or progressive dilation of cysts

- Excretion of blood clots causes renal colic

Question 12

What branch of the circle of willis is most likely to have a berry aneurysm?

Answer 12

1. Anterior communicating artery

2. Middle cerebral artery

Question 13

Who is most likely to have autosomal recessive polycystic kidney disease (ARPKD)?

Answer 13

• Children

Question 14

What do the kidneys look like grossly in ARPKD?

Answer 14

• Enlarged
• Smooth external appearance
• When cut, there are numerous small cysts in the cortex and medulla giving the kidney a sponge like appearance

Question 15

What are the most severe cases of ARPKD? Why?

Answer 15

• Perinatal and neonatal with serious manifestations appearing at birth
• Young infant could quickly succumb to renal failure

Question 16

What is the most common mutation in ARPDK?

Answer 16

• PKHD1 –> highly expressed in adult and fetal kidneys as well as liver and pancreas

Question 17

What does the PKHD1 gene do?

Answer 17

• Encodes fibrocystin –> function unknown but its putative conformational structure indicates it may be a cell surface receptor with a role in collecting duct and biliary differentiation

Question 18

What is a medullary sponge kidney?

Answer 18

• Multiple cystic dilations of the collecting ducts in the medulla

Question 19

Who has medullary sponge kidney?

Answer 19

• Adults and discovered radiographically

Question 20

What does the medullary sponge kidney look like grossly?

Answer 20

• Papillary ducts in the medulla are dilated, and small cysts may be present

Question 21

What is nephronophthisis?

Answer 21

• Group of progressive renal disorders that is characterized by variable number of cysts in the medulla, usually concentrated at the corticomedullary junction

Question 22

What causes renal insufficiency in nephronophthisis?

Answer 22

• Cortical tubulointerstitial damage

Question 23

What are the three types of nephronophthisis?

Answer 23

1. Sporadic, nonfamilial
2. Familial juvenile nephronophthisis (most common)
3. Renal-retinal dysplasia

Question 24

How are the familial forms of nephronophthisis inherited?

Answer 24

• Autosomal recessive inheritance patterns (usually manifest in childhood)

Question 25

What gene loci are mutated to form the juvenile forms of nephronophthisis?

Answer 25

• NPHP1 to NPHP11

Question 26

How is the diagnosis of nephronophthisis made?

Answer 26

• Disease is strongly considered in children or adolescents with otherwise unexplained chronic renal failure, positive family history, and chronic tubulointerstitial nephritis on biopsy

Question 27

How do children with nephronophthisis usually present?

Answer 27

• First with polyuria and polydipsia (reflect a marked defect in the concentrating ability of renal tubules)
• Sodium wasting and tubular acidosis
• May have extrarenal associations like ocular motor abnormalities, retinal dystrophy, liver fibrosis, and cerebellar abnormalities

Question 28

When are simple cysts usually found?

Answer 28

• Postmortem

Question 29

What can happen to simple cysts?

Answer 29

• Hemorrhage into them may cause sudden distention and pain

- Calcification of the hemorrhage may give rise to bizarre radiographic shadows

Question 30

What do renal cysts look like on radiologic studies?

Answer 30

• Smooth contours, and are almost always avascular

- Give fluid rather than solid signals on U/S