Genetic Flashcards
msot common inherited renal disease
AD polycystic kidney disease
at what age does ADPKD present?
bimodal: 20-50 or childhood
ADPKD represents ___% of ESRD in the US
2-3%
ADPKD is usually (bilateral/unilateral)
bilateral (15% asymmetric, usually in kids)
typical adult presentation of ADCKD
polyuria, hematuria, flank pain, HTN
pathogenesis of HTN in ADPKD
cysts compress surrounding parenchyma, activating RAAS
relatively common complications of ADPKD
cystic lesions of other organs (liver, pancreas, lung) and berry aneurisms
___% of individuals with ADPKD remain undiagnosed
50%
diagnosis of ADPKD
combination of ultrasound results, positive family history, age, and cysts in other organs (genetic testing identifies only 70%)
polycystin-1 is a _____ that regulates ____ influx in renal tubular cells, thus inhibiting cell proliferation
primary cilium transmembrane glycoprotein; calcium
cysts formed in ADPKD are classified as?
benign renal tubular neoplasms
mechanism of cyst development in ADPKD
two-hit mechanism
how do cysts cause renal failure?
expand and destroy normal functioning renal tissue, also stimulate RAAS
mutations in (PKD1/PKD2) are associated with an earlier disease onset and more severe disease course
PKD1
first line treatment of ADPKD
ACEI or ARB + salt restriction to control BP
experimental treatment of ADPKD
avoid stimuli for cAMP (caffeine, theophylline), decrease arginine vasopressin (high water intake, inhibitor such as tolvaptan)
inheritance pattern of Alport’s syndrome
x-linked in 85% of cases
symptoms of Alport’s syndrome
anything from benign hematuria to nephritis, progressive hearing loss
pathogenesis of Alport’s syndrome
aberrant structure/function of collagen 4, a critical component of the GBM and cochlea
Alport’s syndrome progresses to renal failure and HTN in?
X-linked males, AR males/females, X-linked females with skewed X inactivation
there is tremendoes overlap between Alport’s disease and this disease
thin basement memrane disease (benign familial hematuria)
secondary signs of Alport’s disease (not sensitive)
lenticonus, leiomyomas
heterogeneity of Alport’s syndrome is dictated by?
the type of mutation (rather than the gene) - nonsense, missense, frameshift, and large deletions are worse than splice variants and intronic mutations
diagnosis of Alport’s
skin or kidney biopsy, genetic testing, IF staining
AR Alport’s results in staining of the?
Bowman’s capsule (5-5-6 monomer is here)
treatment of Alport’s syndrome
kidney transplant works well (unless anti-GBM disease develops)
inheritance pattern of Fabry’s disease
X-linked
pathogenesis of Fabry’s disease
deficiency of alpha-gal leads to accumulation of glycosphingolipids in the cell with irreversible damage
early clinical manifestations of Fabry disease
acroparesthesias, GI sx, hypohydrosis, angiokeratomas (in 40%), hearing loss, corneal verticillata (diagnostic)
late clinical manifestations of Fabry disease
proteinuria and ESRD; cardiac: LVH, atherosclerosis, conduction abnormalities, and arrhythmias (can have ‘renal’ or ‘cardiac’ variants)
causes of variation within Fabry disease
X-inactivation in females, epigenetic factors, different mutations
diagnosis of Fabry disease
first requires suspicion of the disease (hardest part), angiokeratoma and corneal verticillata are diagnostic, measurement of alpha-gal activity works very well in males, genetic testing in women can help
treatment of Fabry disease
IV enzyme replacement therapy (agalsidase)
side effects of agalsidase therapy
infusion-related rxns (fever, chills, rigors); antibody formation
