B69 developmental abnormalities and cystic disease of the kidneys

Question 1

What are the Developmental Kidney abnormalitites?

Answer 1

1. Complete or bilateral agenesis, rare
   
   • causes embryonic death preceeded by oligohydramnios no/low amnionic fluid because the fetus is not excreting any urine.
2. Unilateral agenesis or hypoplasia
   
   • No significant symptoms if second kidney is in tact
   • As adults, there is increased rates of hypertension
3. Ectopic kidney
   
   • most commonly in the pelvis
   • predisposed to recurrent pyelonephritis due to ureter displacement and backflow.
4. Horse shoe kidney
   
   • a common disorder, seen in ~ 1 in 400.
   • also associated with trisomy 18
   • are usually fused at the lower pole of kidneys, and so ureters must pass over the bottom half of them.
   • most often asymptomatic and normally functional
   • problems are due to abnormal ureter placement that may cause obstruction and hydronephrosis
5. Duplicated ureter
   
   • ​​is the most common kidney abnormality, in ~1% of the population and is asymptomatic.
6. Polycystic kidney disease

Question 2

What are the two types of polycystic kidney disease?

Answer 2

1. Autosomal dominant PCKD, single allele, present in middle aged patients as renal failure.
2. Autosomal recessive PCKD, homozygous mutations, presents in fetus or immediately at birth.

Question 3

How does autosomal recessive PCKD present and what is its progression?

Answer 3

Presentation

• In middle aged patients.
• Hematuria, proteinuria, polyuria and hypertension.
• Massive polycystic kidneys, up to 4kg (normal is 150)
• Risk for cysts in other organs, lung pancreas spleen liver
• 4-10% have a Berry aneurysm of the circle of willis
• May present with an event of severe pain due to hemorrhage or obstruction and inflammation.

Progression

• progressive cyst development and expansion eventually destroys kidney parenchyma
• leads to end stage kidney failure
• Requires dialysis until kidney transplant.

Question 4

What causes dominant PCKD?

Answer 4

Mutation to the PKD1 or PKD2 gene, encoding polycystin-1 and 2

It is a membrane associated glycoproteins, involved in the adhesion of tubular epithelium to the ECM.

Causes dysregulated tubule formation and cysts.

PKD2 mutations have a slower progression

Question 5

What causes autosomal recessive PCKD?

Answer 5

Distinct mutation from the dominant type.

Homozygous mutations to the PKHD1 gene, coding for the receptor protein called Fibrocystin. Its function is unclear but it is present in the cilia of tubular epethlium.

This causes dysgenesis of the collecting tubules.

Causes malformation and innumerable small cyst formation 1-2mm, creating a sponge kidney presenting immediately at birth.

Also causes cyst formation in the liver, lung, spleen, and pancreas.

Question 6

What is the progression

Question 7

How does autosomal recessive PCKD present and what is its progression?

Answer 7

Can present: perinatal, neonatal, infantile, or juvenile.

Causes early renal failure or hepatic failure due to cysts.

Survival beyond infancy will progress to liver cirrhosis as well.

Unfortunately no treatment and generally die in infancy.

Question 8

What are the cystic diseases of the kidney?

Answer 8

1. Simple cysts
2. The polycystic kidney diseases
3. Dialysis associated kidney disorder
4. Medullary cystic diseases
   
   • Medullary sponge kidney - common and innocuous, associated with increased renal calculi formation, and appears more often in marfan, ehlers danlos syndromes.
   • Nephronophthisis- medullary cystic disease complex

Question 9

Describe nephronophthisis-medullary cystic disease complex

Answer 9

A rare disease.

Four variants based on time of onset: infantile, juvenile, adolescent, and adult. Juvenile is most common.

• Numerous cysts form at the coritcomedullary junction,
• Kidneys are small and contracted due to chronic tubulo-interstitial nephritis, and progressive interstitial fibrosis.
• Presents with initial polydipsia and polyuria, and progresses to ESRF over 5-10 years.
• ~20% have extrarenal manifestations of the
  
  • retinitis pigmentosa
  • early onset blindness
  • mental retardation
  • liver fibrosis

Question 11

What causes dialysis associated cystic kidney disorder and what is its presentation?

Answer 11

This occurs in patients on dialysis, thus they have a pre-existing end stage kidney disease.

The fibrotic kidney causes compression of in tact tubules, causing dilation.

The cysts are present throughout kidney and may bleed causing hematuria.