Inherited Renal Diseases Flashcards
pdk1 patients vs pdk2 patients
pdk1 present younger and have a worse px
genetic mutations in ADPKD
PD1- chrom 16–>produces polycstin (cell membrane protein that mediates cell-cell/cell-matrix interactins
PKD2- chrom 4- encodes polycstin 2–>role in Ca signaling
extra renal manifestations of ADPCKD
seminal vesicle and/or epidymal cysts are found in 40% of men
htn
hepatic cysts, pancreatic cysts
ADPKD does not develop cysts in
ovaries
ADPKD also manigests as
CT abnormalities
-cardiac valce disease, aortic root dilation, cerebral aneurysms, colonic diverticula
most common cardiac valve abnormality in APCKD
mitral valve prolpase
maturation arrest hypothesis
in addition to first hit of bad genes, epithelial cells from renal cysts have been found to overexpress epithelial growth factor (EGF) receptors–>increase downstream signalt ransduction via MAPK and JAK-STAT pathways–>increased cystic proliferation
CFTR
camp regulated Cl channel implicated in secretory fluid regulation in ADPKD
primary cilium’s job
direct the three-d geometry of development- disruption of this may lead to abnormal morphology of tubules
therapies
block EGFR, JAK-STAT, MAPK/ERK, MTOR
block CFTR and downstream cAMP signal
block vasopressin release/binding to R–>decrease intracell camp
*avoid caffeine–>increases camp
APCKD is a ciliopathy
polycystin 1 and 2 are located on primary cilium, and ARPKD has a PKHD1 mutation–>fibrocystin–also found on primary cilium
mutations in kif31 and ift88
also show issues with synthesis of primary cilia
loss of heterozygosity
patients born with one good gene and are okay until seomething messes up the second normal gene
TSC1 and TSC2
tumor suppressor genes critical for regulation progression through teh cell cycle via effects on mTOR and CDC25C
how does tsc1 and tsc2 work
tsc 1 encodes–>hamartin tsc 2 encodes–>tuberin
hamartin and tuberin combine and downregualate mtor and plk1
if mtor is inhivited
the cell will not progress throug cell cycle
tuberous scleoriss mutatiosn
mutated genes ont sc1 on chrom 9 and tsc2 on chrom 16
tuberous scleoris sresults in
tumors and voluminous cytoplasm in kidneys, skin, cns and heart
renal TS has three forms
renal angiomyolipomas
renal cysts
renal cell carcinoma
2-3% of patients with large genomic deletions of TSC2 will have
adjacent PKD type 1 gene affected leading to combined TS and APCKD
VHL gene
tumor suppressor gene located on short arm of chrom 3
lack of VHL
increase GF including VEGF, PDGF-B, TGFa–>lead to tumor growth
H1F1A
usually these growth factors taht VHL lets happen happen with hypoxia via H1FA
without functional pVHL, H1f1s just produce a shit ton of factors
VHL syndrome and missense mutatiosn
signficantly greater risks for developing pheos
most common lesions of VHL
benign neoplasms called hemangioblastomas (HABs)
HABs
usually present young and are recurrent–>delay surgery until tumor so big it is causing symptoms
second most common VHL tumor
retinal capillary hemangioblastoma
third most common VHL tumor
renal cysts adn clear cell renal cell carcinoma
what do you do with an RCC
watch it carefully- want to preserve kidney fx so weigh surgery only when necessary
transplants last resort because IS treatment makes tumors happy
most common cause of death vhl patients
clear cell renal cell carcinma
all VHL tumors
hemangioblastoma
retinal capillary hemangioblastoa
renal custs and RCC
pheos
all tumors of TS
brain lesions rhabdomyomas angiomyolipomas cysts rcc
characterstic tumor of TS
SGCT–children present with hydrocephalus
CV manifestations TS
coarction of aorta, constriction of major vessels, aneurysms
angiomyolipoma
benihn yumot composed of blood vessels, smooth muscle, and fat
symptoms of angios
usually asymptomatic unless rupture
treatment of angios
surgery
renal artery emboliation
nephrectomy
mtor inhibitors (rapamycin)
patients with TSC may also develop
lympahngioleiomymatosis
cystic disease which affects pulmonary fx
LAM usually presents with
dyspnea or pneumothroax
TSC and derm
hypopihmented macules (ash leaf spots)
angiofibromas in the malar region offace
shagreen pathces over lower trunk
fibrous plaques on forehead
