Renal: Inherited Causes Of Ckd

Front 1

Alport's Syndrome
1) Inheritance
2) Gene product defect

Back 1

1) X- Linked
2) Alpha- 5 subunit of Type IV collagen

There are also AD and AR forms that are the defect ins s and 4 subunits respectively

Front 2

ADPKD
1) Inheritance
2) Gene product defect

Back 2

1) AD
2) Polycystin 1 and 2

Front 3

Fabry's
1) Inheritance
2) Gene product defect

Back 3

1) Xlinked
2)Alpha-galactosidase

Front 4

Primary Hyperoxaluria
1) Inheritance
2) Gene product defect

Back 4

1) AR
2) Various

Front 5

Tuberous Sclerosis
1) Inheritance
2) Gene product defect

Back 5

1) AD
2) Tuberin

Front 6

Wilms tumor
1) Inheritance
2) Gene product defect

Back 6

1) AD
2) WT1, 2

Front 7

ADPKD is a ___1____ disorder caused by a mutation in ____2____

Back 7

1) systemic
2 Polycystin 1 or 2

Front 8

1) Prevalence of ADPKD in US
2) Family history is present in ___2___% of people at first diagnosis

Back 8

1) 1:500
2) 60%

Front 9

Criteria for ADPKD diagnosis
1) under age 30
2) age 30-59
3) mode of diagnosis

Back 9

1) one cyst on each side
2) 2 cysts on each side
3) Ultrasound

Front 10

ADPKD Genetic diagnosis
1) what is needed and what test is done
2) what can make this test a false positive or negative?

Back 10

1) sequencing, need only sample from affected person
2) insignificant mutations and mutations in unseen parts of the gene

Front 11

Why do we care about evaluating for ADPKD in young people?

Back 11

Only whe the are being eval'd as kidney donors

Front 12

1-5) 5 renal symptoms of ADPKD

6-9) 4 extrarenal manifestations od ADPKD

Back 12

1) hematuria
2) cyst belleding
3) cyst infection
4) HTN
5) progressive CKD

6) Berry aneurysms
7) Liver/ovary/panc cysts cysts
8) Mitral valve proplase
9) Diverticulosis

Front 13

What manifestation of ADPKD can mimic kidney stone?

Back 13

Cyst bleeding

Front 14

ADPKD cyst infection is more common in ____1____ because of ____2___

Back 14

1) women
2) ascending infection

Front 15

In ADPKD do we see HTN or decreased GFR first?

Back 15

HTN

Front 16

I see a patient with a hemorrhagic stroke and hemturia, what should i think?

Back 16

ADPKD-- berry aneurysm!!

Front 17

What is the presentation of Liver/ovary/pancreas cysts in ADKD

Back 17

1) no organ dysfunction, may present with pain

Front 18

Does ADPKD affect men or women more?

Back 18

SAME

Front 19

During kidney development, polycystin 1 is localized in the____1___.
In the adult kidney it is found mainly in the ___2___. Her they function in cell-matrix interactions and as _____3____ .

Back 19

1) ureteric bud
2) cell-cell juctions
3) signal transducers

Front 20

second hit hypothesis in ADPKD

Back 20

Polycystin genes inherited ss normal has a high rate of spontaneous mutation, giving the second hit needed for dysfunction. both alleles must be knocked out. AD means that one is KO in germline.

Front 21

Three psteps for cyst formation in ADPKD

Back 21

1) Abnormal cell proliferation
2) Fluid accumulation
3) abnormal ECM metabolism

Front 22

How do ADPKD cysts damage kidneys?

Back 22

distotion of normal tubules and blood vessels

Front 23

Describe how ADPKD which causes cilia dysfunction leads to cyst formation?

Back 23

Normal cilia sense flud flow. Those with defective cilia never sense this flow, so they are always inducing "repair". This is seen as clonal prolieration of the epithelial cell, with fluid secretion. there is also breakdow of cell cycle regulation.

Front 24

How many abnormal polycystin alleles does it take to cause ADPKD

Back 24

Cysts arise by clonal proliferation of cells with two abnormal PKD1 genes

Front 25

Why would we investigate rapamycin as a drug to give in ADPKD?

Back 25

One of the genes upreglated in ADPKD mediated inappropriate "repair" (cyst formation" is mTOR.

Front 26

how does ADPKD cause HTN?

Back 26

Stretches nearby arterioles causing renin and AII release. Also stimulates sympathetic nervous system

Front 27

1) Average age of onset in ADPKD
2) age at which half will develop renal failure
3) poor prognosis is indicated by this co-morbidity
4) other markers of poor prognosis

Back 27

1)45
2) 70
3) HTN
4) black, sickle cell trait, male, large kidneys

Front 28

Compare the outcomes of the PKD1 vs. PKD2 mutations in the course of ADPKD

Back 28

1) PKD2 present later (40% after 60)

Front 29

1)Mainstays of therapy for ADPKD induced CKD
2) A drug in trial is a ___2____ receptor antagonist. The rationale behind this is that it could reduce ___3___ and thus halt cystic cell proliferation

Back 29

1) dialysis and transplant
2) Vasopression (V2)
3) cAMP

Front 30

Also on the DDx fo kindey cyst:
Simple cyst... describe

Back 30

common in aging, thin walled. one or several may be seen.

Front 31

Also on the DDx fo kindey cyst:
Acquired cystic kidney disease...describe

Back 31

multiple bilateral renal cysts in patients after prolonged dialysis. Increases risk of reneal tumor.

Front 32

Also on the DDx fo kindey cyst:
Medullary cystic kidney disease... describe

Back 32

Ad inheirtance
Presents with renal failure in teens or 20s.
Cysts form at corticomedullary juntion.
Salt wasting sometimes seen

Front 33

Medullary cystic kiney disease
1) Inheritance
2) Gene defects
3) age range
4) location of renal cysts

Back 33

1) AD
2) MCKD-1 and 2
3) teens-20s
4) corticomedullary junction

Front 34

1) Alports inheritnace

Renal manifestations of alports
2) in childhood
3) In 20-40s
4) Mid 40s

Back 34

1) X-linked
2) Hematuria in childhood or adolesence
Bad proteinuria by 20-40
Advdnaced CKD in males requiring dialysis or transplatnt by 40s

Front 35

1) Alports defect

Extrarenal manifestations of Alports
2) _____ develops in 90% of pts. by age 30
3) Two possible optical findings
4) Hematologic

Back 35

1) Type IV collagen missing due to mutant alpha-5 subunit
2) Sensorineural hearing loss
3) Cataracts or Anterior lenticonus
4) platelet defects

Front 36

)three subunits in normal adult type IV collagen
2) three subunits in embryonic type 4 collagen in kidney GBM.
3) What is present ins alports?

Back 36

1) alpha 3,4,5
2) Alpha 1,2,2
3) Embryonic

Front 37

What is the only physical finding that is pathognomonic for Alports?

Back 37

Anterior lenticonus (looks like an oil droplet)

Front 38

Can women get Alports?

Back 38

Some female trait carriers can develop kidney failure. much less common than males.

Front 39

A Pt presents with hematuria and ESRD with a family history of hearing loss. Dx?

Back 39

Alports

Front 40

Two ways to biospy for Alports:
1) kidney biopsy shows?
2) what other kind of biposy can we do and what will it show?

Back 40

1) splitting of the lamella densa of the GBM
2) SKin biopsy shows lack of alpha-5 chain

Front 41

What will ALL females with the Alports trait (carrier) show?

Back 41

microscopic hematuria

Front 42

Type IV collage in 4 places...

Back 42

GBM
nephron tubule
epidermis
vestibulocochlear aparatu

Front 43

Why does normal type IV collagen (alpha 3,4,5) hold up better than embryonic type Iv collagen (1,1,2) as is seen in Alport's?

Back 43

greater crosslinking

Front 44

What is the difference between the common X-linked form of alportsad the uncommon AR form?

Back 44

AR has mutant in alpha 3 or 4 subunit of type IV collagen

Front 45

1) All affected mles with Alports will develop...
2) Best Tx
3) What is a complication of this procedure?

Back 45

1) ESRD
2) transplant
3) donor type IV colagen is anovel antigen in this pt.-- causes anti-GBM autoimmunity

Front 46

1) how my benign familial hematuria (THin basement membrane disease) and Alports related?

2) Inheritance?

Back 46

1) it may be the trait-carrier (heterozygous) manifestation of the mutant seen in AR (rare) form of alport where alpha 3 or 4 for subunit is mutant
2) AD (makes sense, think about it)

Front 47

1) Why does fabry's get so much attention
2) inheritance?
3) General type of disease?

Back 47

1) because we have a good Tx!
2) X-linked
3) multi-system lysosomal storage

Front 48

1) Enzyme lost in Fabry's
2) function of the enzyme is to remove the _____1_____ from the ____3____ called __4____.

Back 48

1) alpha-galactosidase-A
2) terminal galactose
3) glycosphingolipid
4) globotriosyl-ceramide

Front 49

1) Renal manifestation of Fabry's disease
2) skin manifestation
3) Cardiac manifestations
4) Optic manifestation

Back 49

1) proteinuria and hematuria with CKD by 50
2) purple papules on lower trunk and genitalia (Angiokeratosis)
3) LVH, CAD, arrhythmias
4) Corneal opacity

Front 50

Diagnosis of Fabrys
1) Alpha-galactosidase A level can be measured in what cells and found to be low??
2) Is this finding seen in female carriers?
3) what may be found in the urine
4) What finding is pathognomionic for Fabry's?

Back 50

1) peripheral WBCs
2) they will be in the lower range of NORMAL
3) ceramide trihexoside and digalactoside
4) Zebra Lamellar bodies on biopsy.

Front 51

1) Tx for Fabry's
2) how often

Back 51

IV alpha-galactosidase A every two weeks

Front 52

Why do we see renal manifestations of sickle cell anemia

Back 52

Becuse the renal medulla is hypoxic and hyprosmolar

Front 53

Inreased GFR
Urine concentration defect
Acidification deect
Hyperkalemia
Hematuria
Papillary necrosis
Proteinuria
CKD

.... are all possible renal problems caused by...

Back 53

SCD (Hb-SS)

Front 54

SCD can cause _____kalemia

Back 54

hyper

Front 55

Does the increased RBF and GFR caused by SCD reduce with transfusion?

Back 55

NOPE

Front 56

1) What is the most common renal defect seen in SCD and how is it causes.

This is not seen in children under 10

2) Up to age 15 we can reverse this problem with....

Back 56

1) renal concentration defect. Cannot concentrate above 400 mosm/L. This is due to loss of the vasa recta due to ischemia and infarction
2) Transfusion

Front 57

Highest Uosm achievable by a 20 YO with SCD

Back 57

400 mosm/L

Front 58

SCD can cause a metabolic ____osis and _____kalemia to ischemia of the distal nephron

Back 58

1) acidosis
2) hyper

Front 59

What is the Tx for SCD induced acidosis, hyperkalmeia, and hematuria?

Back 59

hydration, transfusion, and alklaninization of the urine.

Front 60

Painless, gross hematuria in patient with SCD suggests what process?

Back 60

Papillary necrosis (15-36%)

Front 61

What pathologic finding is associated with nephrotic range proteinuria in SCD?

Back 61

Focal, segmental, glomerulosclerosis.