Inherited cystic renal disease

Question 1

Autosomal dominant polycystic kidney disease (ADPKD)

Answer 1

• Characterized by intraparenchymal renal cysts that are lined by single layer of epithelial cells
• ADPKD mutations may be in 1 of 2 places, but most of the mutations are on chrom 16p13.3 (APKD1/2)
• The gene mutated (polycystin) mediates interaction btwn ECM and cells
• Cysts are in medulla and cortex, kidneys are enlarged
• Dx of ADPKD is usually made via ultrasound

Question 2

Pathology of ADPKD

Answer 2

• First there is local dilation of renal tubule, which expands by proliferation of a monoclonal cell w/ the PKD1 mutation
• The epithelial cells then pump fluid into the space creating a cyst and loss of functional renal parenchyma
• For this fluid to be pumped into the lumen the cells’ polarity must be flipped (NKCC on basolateral side, CFTR and AQP on apical side allowing Cl and H2O to accumulate in the lumen)
• There is increased CFTR activity from increased cAMP, which is elevated due to lack of functional PC1-> decreases IC Ca (Ca enters thru PC1)-> increase in IC cAMP
• This process of forming a cyst requires 2 hits to PC1

Question 3

Manifestation of ADPKD

Answer 3

• Sx start in 2nd-3rd decade and usually present w/ flank pain due to hemorrhage, pyelonephritis and hematuria, HTN or renal insufficiency, inability to concentrate urine, renal failure
• HTN results from activation of RAAS due to cyst stretching and attenuation of intrarenal vessels
• The kidneys are irregular, large, and palpable
• Complications include UTI, perinephric abscess, infected cyst, hemorrhage of cyst, renal calculi, and obstruction
• Extra renal complications: intracranial aneurysms and cerebrovascular events (berry aneurysms), liver cysts (w/ normal liver fxn but possible ascites), colon diverticular, ao regurg, cysts in pancreas and ovaries, mitral valve prolapse

Question 4

Alport’s disease

Answer 4

• A deficiency in a5 (and a3/a4) collagen, X-linked (males) present with hematuria
• Most will end up on dialysis/ESRD
• Tx recipients may develop anti-GBM since their body is not accustomed to having an a5 antigen, thus they will make Abs against the new kidney’s BM
• Alport’s associated w/ deafness, and blindness/lens abnormalities

Question 5

Alport’s vs thin BM

Answer 5

• Thin BM is mutation in collagen a4 resulting in diffuse attenuation of GBM
• Most often in females, only manifestation is hematuria
• Alport’s syndrome is mutations in a3, a4, a5 collagen that is almost exclusively males (X linked)
• Pts present w/ hematuria and can also have deafness and eye problems

Question 6

Autosomal recessive PKD (ARPKD)

Answer 6

• More severe, cyst formation occurs in utero
• Infants present w/ worsening renal failure, HTN
• May present w/ potters syndrome
• Associated w/ congenital hepatic fibrosis and hepatic cyst

Question 7

Medullary cystic kidney disease

Answer 7

-Cysts form in medulla, kidneys are shrunken (not enlarged like in PKD) w/ parenchymal fibrosis