PCKD + Diuretics

Question 1

Genetics

Answer 1

• autosomal dominant
• most common inherited renal disease
• mutation in PKD1 and PKD2 (polycistin)
• 10-15% de novo mutations
• mosaicism –>milder disease

PKD1 is more severe than PKD2, ESRF by 60

Question 2

Clinical presentation

Answer 2

Renal related

• HTN
• Hematuria
• Renal failure
• Flank pain
• Chronic pain

Extra-renal

• Cerebral aneurysm
• Hepatic cysts
• Panc cysts
• Seminal valve cysts
• Cardiac valve disease

Question 3

Diagnosis

Answer 3

1. Family history + about 3 cysts under 40 or 4 from 40-60
2. No family hx - >10 cysts each + bilateral renal enlargement

Can use USS, MRI is better

Question 4

Management

-HTN, Diet, Lipid, Meds

Answer 4

1. HTN - ACEi or ARB
2. Diet - low salt
3. Fluid - aim 3L/day
4. Medications - Tolvaptan

Question 5

Tolvaptan

MOA
A/E

Answer 5

vasopressin receptor antagonist (aka anti ADH) –> diuresis ++ –> lower cyst burden + decrease cAMP

A/E - AKI, polyuria, polydipsia, nocturne, LFT derangement, serum Na abnormalities

Question 6

Prognosis

Answer 6

• most die from CVD
• 50% ESRF by 60

Poor prognosis a/w

• early onset GRF decline
• High Na intake
• early HTN
• PKD1
• Proteinuria
• elevated copeptin
• Fly hx

Question 7

Diuretics

Types and Location

Answer 7

COLT PEE

(Carbonic anhydrase inhibitor, osmotic diuretic, loop diuretic, thiazide, potassium sparing)

C - prox conv tubule
O - prox conv tubule
L - loop of Henle
T - distal cone tubule
P - collecting duct

Question 8

Carbonic anhydrase inhibitor

Answer 8

• inhibits H+ HCO3 –> H20 + CO2 which defuses across membrane
• inhibition causes Na to be excreted

Question 9

Osmotic diuretic

Answer 9

Mannitol

Non reabsorbable solute

Question 10

Loop diuretic

Answer 10

blocks Na/Cl/K symporter

• needs to be “filtered” by glomerulus so needs good kidney function to work
• binds ++ to protein, doesn’t work as well in proteinuria
• causes ++ Na in urine ==> hypertrophy in DTC to compensate, eventually becomes less effective
• good to add HCT

Question 11

Thiazide

Answer 11

• inhibits Na abs via Na+Cl- in DCT

- needs to be “secreted” so needs good renal function

Question 12

Potassium sparing

Answer 12

1. Spiro or Elperone - anti aldosterone
   - inhibits Na/K channel
2. Amiloride or triamterene - blocks ENAC channel
   * trimethoprim - blocks ENA