Polycystic Kidney Disease

Question 1

Genes for Polycystic Kidney Disease

Answer 1

PKD 1 - (polycystin 1)
PKD 2 - (polycystin 2)

+ some others (GANAB, DNAJB11)

Question 2

Prevelance of PKD?

Answer 2

~1:1000

Question 3

Genetic expression of PKD?

Answer 3

Autosomal dominant

Question 4

Percentage of PKD patient with/ without FHx of PKD

Answer 4

10-15% no FHx

• De novo mutations
• Mosaicism
• Mild disease (e.g. PKD2 or non-truncating PKD1)
• No parental information

Question 5

Which PKD (1 vs 2) is more severe?

Answer 5

PKD much more severe

Question 6

When is kidney function imapired in PKD?

Answer 6

Usually in 4th decade life

50% ESKD by 60

Question 7

RFs for progresive PKD?

Answer 7

• Genetics (major factor) e.g. PKD1, truncating
• Male
• Early onset of Sx
• Family Hx of early ESKD (before age 55)
• Kidney size
• Hypertension
• Proteinuria

Question 8

What other organs with cysts in PKD?

Answer 8

liver, pancreas, spleen, epididymis

Question 9

RCC in PKD?

Answer 9

No increased risk but harder to diagnosis on imaging

Question 10

Renal manifestation of PKD?

Answer 10

• Hypertension (often before decline in eGFR)
• Haematuria (35 – 50%)
• Proteinuria (less common, prro prognosis)
• Renal failure
• Flank pain (Cyst haemorrhage, Cyst infection, Calculi, UTI)
• Chronic pain syndrome

Question 11

Important extra-renal manifestations for PCKD?

Answer 11

• Cerebral aneurysms

• Cardiac valve disease (MVP and AR most common, less freq MR and TR)
• Aortic dissection / aneurysm
• Hepatic cysts
• Pancreatic cysts (a/w IPMN)
• Seminal vesicle cysts
• Colonic and duodenal diverticulae
• Abdominal wall and inguinal hernia

Question 12

Patient’s with PCKD to screen for cerebral aneurysms?

Screenign methos

Answer 12

High risk patient’s only

• prior rupture
• FHx
• Neuro Hx
• High risk job (e.g. flying)
• prior to surgeries

Screen with MRI (contrast) or CT A)

Question 13

Patient’s with PCKD to screen for cerebral aneurysms?

Screenign methos

Answer 13

High risk patient’s only

• prior rupture
• FHx
• Neuro Hx
• High risk job (e.g. flying)
• prior to surgeries

Screen with MRI (contrast) or CT A)

Question 14

Screening test for PCKD

Answer 14

US
or MRI - more sensiteve than US

If very high risk:
- genetic testing

Question 15

Autosomal Dominant Tubulointerstitial Kidney disease

Answer 15

• formally known as “medullary cystic kidney”
• dilation of the medullary collecting ducts, progressive fibrosis / renal failure,
• kidneys not usually enlarged, cysts not always present (but if they are, the renal cortex is spared as opposed to PCKD),
• bland urine sediment

Question 16

Main differnece between Autosomal Dominant ve Recesive Polycystic Kidney Diseaes>

Answer 16

• more severe disease (30% fatal at birth),
• usually presents in older children / young adults,
• they have congenital hepatic fibrosis and portal HTN

Question 17

Management of polycystic Kidney disease?

Answer 17

Manage hypertension (mortality improved more than in non-PCKD)
- ACEi or ARB

Decrease Na intake

increase Fluid intake (>3L/ day)

Lipid control

?Caloric restriction

Tolvaptan

Question 18

Tolvaptan mechanism

Answer 18

Vasopressin V2-receptor antagonist

Question 19

Starting tolvaptan

Answer 19

• Start 45 mg mane / 15 mg eight hours later
• Increase dose every 1-4 weeks (as tolerated, to max 90 / 30)
• Degree of reduction in urinary osmolality a/w reduction in cyst growth (aim <280 mOsm/kg)
• If hypernatremic - enhance hydration or reduce dose, If hyponatremic do opposite

Question 20

Adverse effects of tolvaptan (in PCKD)

Answer 20

• Polydipsia, polyuria, nocturia
• decrease eGFR (small decline acceptable)
• Abnormal LFTs (in 5%)
• Hypernatremia (enhance hydration or reduce dose)

Question 21

Major cause of death in patients with PCKD?

Answer 21

Cardiovascular death