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Question 1

Most common gene mutation in PKD

Answer 1

PKD1 - polycystin 1 on x/some 16 (80%)

PKD2 (15%)

Question 2

Types of mutation in PKD gene & which is worse

Answer 2

Truncating (2/3) - stop from nonsense (or frameshift which then early stops) - WORSE
Non truncating (1/3) - milder dis

AD but 10% no FHx (de novo or mosiacsim or mild dis)

Question 3

PKD RF for progressive dis

Answer 3

Genetics (PKD1, truncating) - major
Male, early onset, FHx
HTN, 
proteinuria (should be blood not protein so bad if is!)
Kidney size

Question 4

PKD assoc dis

Answer 4

1) Cerebral aneurysms - hence BP /lipid control, don’t smoke (usu MCA) 5x risk
- only screen high risk or pre-major surgery

2) hepatic cysts (scan liver if abdo sx)
3) Cardiac valve dis - MVP & AR due to AR dilatation)

Not assoc w/ RCC but harder to see

Question 5

PKD on USS - criteria

Answer 5

NO PKD: if MRI with <5 cysts in young person, or No cysts on USS by 40yrs

FHx + (3-B24) on USS

• 15-40 3+ cysts
• 40-60 bilateral 2+ cysts
• > 60 bilateral 4+ cysts

FHx -
- 10+ cysts bilaterally

Question 6

PKD - indications for genetic testing

Answer 6

disconcordance b/w renal imaging & GFR or atypical radiology
If a LRTD
No FHx
Family planning

Question 7

PKD - management

Answer 7

1st line: ACE/ARB
- Increase fluid >3L (aim <280mOsm) & reduce Na aim 2.5g
- Lipid control, improve CV RF
(stop diuretics)

Tolvaptan: ADH blocker! + >5L water

Low osmol diet (Esp at night)

Question 8

Tolvaptan - MoA outcomes

Answer 8

PKD cyst seems to respond to upregulation of cAMP.
Blocking ADH means you pee water but improves cysts

• earlier started the better (anyone w/ GFR<90ml and >5ml/yr or >12.5ml over 5yrs)
• Benefits are cumulative & sustained
• slows growth of kidneys, preserves GFR & reduces pain

Somatostatin analogies slow growth but dont preserve GFR

Question 9

Tolvaptan - PP

Answer 9

Dose twice daily (more in AM) increasing every few wks

Aim hypotonic urine <280mOsm.
eGFR will initially decline ~7%

Monitor serum Na

• if increasing, increase water (or dec dose),
• if decreasing, increase dose (or reduce hydration)

AbN LFTs in 5% (measure monthly for 18m & stop if ALT>3x ULN)

Question 10

Diff b/w NS & GN

Answer 10

NS: podocyte rather than cellular proliferative
Prot: >3g/day or >300mg/mmol spot (ie divide by 100)
Hypoalb, oedema
Hyperlipidaemia
(VTE risk, renal fxn often preserved)

GN: inflammation of glomuerular capillaries - proliferation of cells/leukocyte infiltration (damage to basement mmb, mesangium or capillary endothelium)

• haematuria (RBC casts)
• HTN
• renal impairment

Question 11

NS - most common in 20s, 50s, 80s

Answer 11

All ages FSGS most common
Diab nephropathy peaks 50-70s
Membranous floats 2nd in younger ppl, 3rd otherwise
MCD in kids & >70s, amyloid

Question 12

GN - most common in 20s, 50s, 80s

Answer 12

20s: SLE nephritis, with IgA 2nd
50s: SLE, IgA & ANCA all similar
80s: ANCA by far, then IgA, then SLE with others including Alport

Question 13

Alport syndrome - inheritance & gene typically

Answer 13

Type 4 collagen protein genes - diff chains
COL4A5 most common - X linked recessive
Females due to lyonization can have sx still
Truncating worse.
Can have 2 variants

Question 14

Alport syndrome - presentation

Answer 14

Progressive renal failure - transplant required
- haematuria by age 10yrs usu

+ senosineural hearing loss (bilateral, high freq)
+ ocular (conical protusion on lens - anterior lenticonus, is pathognomic) - present in 25%

Question 15

Alport syndrome - Rx

Answer 15

Monitor from 1 yr in high risk
ACE (potentially dual ARB if still proteinuria)
Tx