Genetic

Question 1

msot common inherited renal disease

Answer 1

AD polycystic kidney disease

Question 2

at what age does ADPKD present?

Answer 2

bimodal: 20-50 or childhood

Question 3

ADPKD represents ___% of ESRD in the US

Answer 3

2-3%

Question 4

ADPKD is usually (bilateral/unilateral)

Answer 4

bilateral (15% asymmetric, usually in kids)

Question 5

typical adult presentation of ADCKD

Answer 5

polyuria, hematuria, flank pain, HTN

Question 6

pathogenesis of HTN in ADPKD

Answer 6

cysts compress surrounding parenchyma, activating RAAS

Question 7

relatively common complications of ADPKD

Answer 7

cystic lesions of other organs (liver, pancreas, lung) and berry aneurisms

Question 8

___% of individuals with ADPKD remain undiagnosed

Answer 8

50%

Question 9

diagnosis of ADPKD

Answer 9

combination of ultrasound results, positive family history, age, and cysts in other organs (genetic testing identifies only 70%)

Question 10

polycystin-1 is a _____ that regulates ____ influx in renal tubular cells, thus inhibiting cell proliferation

Answer 10

primary cilium transmembrane glycoprotein; calcium

Question 11

cysts formed in ADPKD are classified as?

Answer 11

benign renal tubular neoplasms

Question 12

mechanism of cyst development in ADPKD

Answer 12

two-hit mechanism

Question 13

how do cysts cause renal failure?

Answer 13

expand and destroy normal functioning renal tissue, also stimulate RAAS

Question 14

mutations in (PKD1/PKD2) are associated with an earlier disease onset and more severe disease course

Answer 14

PKD1

Question 15

first line treatment of ADPKD

Answer 15

ACEI or ARB + salt restriction to control BP

Question 16

experimental treatment of ADPKD

Answer 16

avoid stimuli for cAMP (caffeine, theophylline), decrease arginine vasopressin (high water intake, inhibitor such as tolvaptan)

Question 17

inheritance pattern of Alport’s syndrome

Answer 17

x-linked in 85% of cases

Question 18

symptoms of Alport’s syndrome

Answer 18

anything from benign hematuria to nephritis, progressive hearing loss

Question 19

pathogenesis of Alport’s syndrome

Answer 19

aberrant structure/function of collagen 4, a critical component of the GBM and cochlea

Question 20

Alport’s syndrome progresses to renal failure and HTN in?

Answer 20

X-linked males, AR males/females, X-linked females with skewed X inactivation

Question 21

there is tremendoes overlap between Alport’s disease and this disease

Answer 21

thin basement memrane disease (benign familial hematuria)

Question 22

secondary signs of Alport’s disease (not sensitive)

Answer 22

lenticonus, leiomyomas

Question 23

heterogeneity of Alport’s syndrome is dictated by?

Answer 23

the type of mutation (rather than the gene) - nonsense, missense, frameshift, and large deletions are worse than splice variants and intronic mutations

Question 24

diagnosis of Alport’s

Answer 24

skin or kidney biopsy, genetic testing, IF staining

Question 25

AR Alport’s results in staining of the?

Answer 25

Bowman’s capsule (5-5-6 monomer is here)

Question 26

treatment of Alport’s syndrome

Answer 26

kidney transplant works well (unless anti-GBM disease develops)

Question 27

inheritance pattern of Fabry’s disease

Answer 27

X-linked

Question 28

pathogenesis of Fabry’s disease

Answer 28

deficiency of alpha-gal leads to accumulation of glycosphingolipids in the cell with irreversible damage

Question 29

early clinical manifestations of Fabry disease

Answer 29

acroparesthesias, GI sx, hypohydrosis, angiokeratomas (in 40%), hearing loss, corneal verticillata (diagnostic)

Question 30

late clinical manifestations of Fabry disease

Answer 30

proteinuria and ESRD; cardiac: LVH, atherosclerosis, conduction abnormalities, and arrhythmias (can have ‘renal’ or ‘cardiac’ variants)

Question 31

causes of variation within Fabry disease

Answer 31

X-inactivation in females, epigenetic factors, different mutations

Question 32

diagnosis of Fabry disease

Answer 32

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

Question 33

treatment of Fabry disease

Answer 33

IV enzyme replacement therapy (agalsidase)

Question 34

side effects of agalsidase therapy

Answer 34

infusion-related rxns (fever, chills, rigors); antibody formation