Cystic Diseases of the Kidney Flashcards
What is autosomal dominant polycystic kidney disease (ADPKD)?
- Hereditary disorder characterized by multiple expanding cysts that ultimately destroy the renal parenchyma anc cause renal failure
Who is most likely affected by ADPKD?
- Adults
- Renal function is fine until the fourth or fifth decade
How do individuals genetically acquire ADPKD?
- 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
What does the PKD1 gene encode for?
- A large integral membrane protein named polycystin-1 (which is expressed in tubular epithelial cells, particularly those of the distal nephron)
What happens if PKD1 is mutated?
- It accounts for 85% of the cases of ADPKD
What does the PKD2 gene encode for?
- Polycystin-2 which is an integral membrane protein that is expressed in all segments of the renal tubules and in many extrarenal tissues
What does polycystin-2 do?
- Functions as a Ca2+ permeable cation channel
What do polycystin-1 and polycystin-2 do together?
- 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
What does increased calcium do due to mutated PKD1 and PKD2 genes?
- Stimulate proliferation and secretion from epithelial cells lining the cysts, which together result in progressive cyst formation and enlargement
What is the clinical presentation of ADPKD?
- 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
What causes the pain felt in ADPKD?
- Hemorrhagic or progressive dilation of cysts
- Excretion of blood clots causes renal colic
What branch of the circle of willis is most likely to have a berry aneurysm?
- Anterior communicating artery
2. Middle cerebral artery
Who is most likely to have autosomal recessive polycystic kidney disease (ARPKD)?
- Children
What do the kidneys look like grossly in ARPKD?
- Enlarged
- Smooth external appearance
- When cut, there are numerous small cysts in the cortex and medulla giving the kidney a sponge like appearance
What are the most severe cases of ARPKD? Why?
- Perinatal and neonatal with serious manifestations appearing at birth
- Young infant could quickly succumb to renal failure
What is the most common mutation in ARPDK?
- PKHD1 –> highly expressed in adult and fetal kidneys as well as liver and pancreas
What does the PKHD1 gene do?
- 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
What is a medullary sponge kidney?
- Multiple cystic dilations of the collecting ducts in the medulla
Who has medullary sponge kidney?
- Adults and discovered radiographically
What does the medullary sponge kidney look like grossly?
- Papillary ducts in the medulla are dilated, and small cysts may be present
What is nephronophthisis?
- Group of progressive renal disorders that is characterized by variable number of cysts in the medulla, usually concentrated at the corticomedullary junction
What causes renal insufficiency in nephronophthisis?
- Cortical tubulointerstitial damage
What are the three types of nephronophthisis?
- Sporadic, nonfamilial
- Familial juvenile nephronophthisis (most common)
- Renal-retinal dysplasia
How are the familial forms of nephronophthisis inherited?
- Autosomal recessive inheritance patterns (usually manifest in childhood)
What gene loci are mutated to form the juvenile forms of nephronophthisis?
- NPHP1 to NPHP11
How is the diagnosis of nephronophthisis made?
- Disease is strongly considered in children or adolescents with otherwise unexplained chronic renal failure, positive family history, and chronic tubulointerstitial nephritis on biopsy
How do children with nephronophthisis usually present?
- 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
When are simple cysts usually found?
- Postmortem
What can happen to simple cysts?
- Hemorrhage into them may cause sudden distention and pain
- Calcification of the hemorrhage may give rise to bizarre radiographic shadows
What do renal cysts look like on radiologic studies?
- Smooth contours, and are almost always avascular
- Give fluid rather than solid signals on U/S
