Congenital Renal Disease - Sujeet

Question 1

What are ducts of Bellini (aka papillary ducts)?

Answer 1

The largest collecting ducts that smaller ducts empty into. Ducts of Bellini empty into the renal calyces.

Question 2

Which cells produce and maintain the GBM: glomerular endothelial cells or podocytes?

Answer 2

glomerular endothelial cells

Question 3

What type of collagen makes up the GBM?

Answer 3

Type IV collagen

Question 4

Which parts of the glomerular filtration barrier (endothelial cells, GBM, podocytes) are negatively charged?

Answer 4

All three are negatively charged

Question 5

What notable protein can be found in mesangial cells?

Answer 5

Myosin filaments (they are specialized SMCs)

Question 6

Horseshoe Kidney

1. How common is it?
2. Where do most fusions occur?
3. What do patients with this disorder have an increased risk of?
4. What other condition does this disorder show an increased incidence with?

Answer 6

Horseshoe Kidney

1. Most common congenital kidney disorder
2. 90% at lower pole
3. Increase risk of kidney stones and infections
4. Increased incidence with Turner’s Syndrome

Question 7

Name five cystic renal diseases.

Answer 7

1. Renal Dysplasia
2. Autosomal Recessive Polycystic Kidney Disease (ARPKD)
3. Autosomal Dominant Polycystic Kidney Disease (ADPKD)
4. Medullary Sponge Kidney
5. Acquired Cystic Disease

Question 8

Renal Dysplasia

1. How common is it?
2. Is it unilateral or bilateral?
3. How can it be detected?
4. How does it appear?

Answer 8

Renal Dysplasia

1. 1 in 4,300 live births
2. Either. (Wiki) ~20-35% are bilateral cases. Bilaterality more common in females. Severe bilateral dysplasia is incompatible with life.
3. Detect via prenatal ultrasound or by a palpable mass. Many go undetected into adulthood.
4. Multicystic appearance

Question 9

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. How common is it? What ethnicity is it most common in?
2. How serious is it?
3. What gene, on which chromosome, is associated with ARPKD?

Answer 9

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. Rare (1 in 20,000). More frequent in caucasians.
2. Very. Perinatal mortality is 30-50%
3. PKHD1 gene, on chromosome 6p21

Question 10

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. What maternal condition is ARPKD associated with? What consequences does this condition have on the infant?
2. How is it diagnosed?
3. What extrarenal manifestations does ARPKD have?

Answer 10

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. Maternal oligohydramnios. This causes:
   
   • Potter’s facies
   • Pulmonary hypoplasia
2. Dx in utero with ultrasound:
   
   • oligohydramnios
   • hyperechoic kidneys
   • decreased urine in fetal bladder
3. Extrarenal:
   
   • Hepatic fibrosis
   • Cholangitis (common bile duct infection)
   • Portal hypertension
     
     • Varices
     • GI bleeding

Question 11

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. What is the gross morphology?
2. What is the microscopic morphology?

Answer 11

Autosomal Recessive Polycystic Kidney Disease (ARPKD)

1. Gross: Smooth kidney with numerous small cysts
   
   • cysts are cortical and medullary
   • cysts are cylindrical and extend radially through the cortex
2. Microscopic: Cysts lined by cuboidal epithelium - may see epithelial hyperplasia
   
   • glomeruli are normal

Question 12

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

1. How common is it? How common is having family Hx?
2. What two genes (on which chromosomes?) can lead to ADPKD when either is mutated?
3. Which mutation is worse?

Answer 12

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

1. More common than recessive variant; 1:400-1000
   
   • Family Hx absent in 25-40% (new mutations)
2. Mutations:
   
   • PKD1 gene on chr. 16 (90%)
   • PKD2 gene on chr. 4 (10%)
3. Pts with PKD1 mutations progress to renal failure at earlier ages

Question 13

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Describe the morphology.

Are the nephrons themselves affected?

Answer 13

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Morphology:

• Abnormal epithelial cell differentiation
  
  • Highly proliferative
• Secretion of fluid into cysts
  
  • loss of connections to functional nephrons
• Abnormal ECM
• Interstitial fibrosis

1-2% of nephrons show cystic dilatation

Question 14

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Name six renal manifestations of ADPKD.

Answer 14

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

1. Hematuria w/ mild proteinuria
2. Hypertension
3. Progressive renal failure
   
   • ESRD by age 57-73 in 50% of pts
4. Infections
5. Stones
6. Pain

(EVERYTHING BAD)

Question 15

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Name six extrarenal manifestations of ADPKD.

Answer 15

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

1. Hepatic cysts (40%)
2. **Intracranial (Berry) aneurysms (10-30%) **
   
   • ​​Can also see aortic, coronary aneurysms
3. Cardiac valve problems
4. Hernias
5. Pancreatic cysts
6. IVC thrombosis

Question 16

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

How does ADPKD typically present?

What are the diagnostic criteria for ADPKD for an individual with family history?

Answer 16

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• Flank pain
• Hematuria
• Multiple, bilateral cyts incidentally noted during imaging

Dx criteria becomes more strict with age:

• Age <30: At least 2 cysts
• Age 30-59: At least 2 cysts in each kidney
• Age >60: At least 4 cysts bilaterally

Question 17

​Autosomal Dominant Polycystic Kidney Disease (ADPKD)

What are the treatment goals for ADPKD?

Answer 17

​Autosomal Dominant Polycystic Kidney Disease (ADPKD)

• Slow progression to ESRD
  
  • BP control
  • Treat infections
• Manage extrarenal manifestations
• Control pain
• Dialysis or transplant when necessary

Question 18

Medullary Sponge Kidney

1. How is it inherited?
2. How does the kidney appear on pyelogram?
3. What is the microscopic morphology?
4. What risks does it predispose to?

Answer 18

Medullary Sponge Kidney

1. No inheritence pattern
2. Spongy on pyelogram
   
   • Can see medullary cysts (appear brighter than normal tissue)
3. Cystic dilation of medullary and papillary (Bellini) collecting ducts
4. Risks:
   
   • Recurrent UTIs
   • Kidney stones
   • Hematuria

Question 19

Acquired Cystic Disease

1. How is it acquired? How common is it via this method?
2. How does it present?
3. What is it a risk factor for?

Answer 19

Acquired Cystic Disease

1. Develops in 50% of pts on dialysis.
   
   • Greater risk with more years on dialysis
2. Usually asymptomatic, but may present with bleeding or pain
3. Increased incidence of renal cell carcinoma

Question 20

Acquired Cystic Disease

1. What do the cysts look like?
2. In what arrangement are they found?
3. Where in the kidney are they found?

Answer 20

Acquired Cystic Disease

1. Clear, fluid-filled cysts
2. Uni- or multilocular (as opposed to throughout entire kidney, like in AD/AR PKD)
3. Usually cortex, sometimes going down into medulla

Question 21

Name four indications for renal biopsy.

Answer 21

1. Persistent glomerular hematuria
2. Persistent nephrotic range proteinuria
3. Unexplained renal failure
4. Renal transplant rejection

Question 22

Name two contraindications for renal biopsy.

Answer 22

1. Bleeding disorders (or pt is significantly anticoagulated)
2. Anatomic abnormalities (do ultrasound first)

Question 23

Name four potential complications of renal biopsy.

Answer 23

• Self-limited gross hematuria (10%)
• Hematoma formation (80%)
• Hemorrhage (1-2%)
  
  • 0.3% require surgical correction
• Death (1 in 8000)

Question 24

1. What is the “Full House” stain on direct IF microscopy?
2. What condition is it associated with?

Answer 24

1. Positive stains for IgG, IgA, IgM, C3, and C1q
   
   • (3 Igs, 2 C’s → “Full House” of immune complex deposition)
2. Indicates Lupus nephritis

Question 25

1. What type of study is required to observe podocyte abnormalities?
2. Diagnosis of what renal disease therefore relies on this type of study and why?

Answer 25

1. Electron microscopy
2. Minimal Chance Disease - noting the **effacement and **fusion of podocyte foot processes **is the ONLY way to definitely diagnose the disease!
   
   • (Fun fact: the disease got its name because for years, scientists could not find any pathological morphology using light or IF microscopy)