PKD - how common - why important

- 1/1000 live births - most end up on dialysis or kidney transplant - 5% end up with ESRD - most common life-threatening inherited renal disease - fourth leading cause of ESRD after DM, HTN, glomerulonephritis

- group of monogenic disorders - characterized by propensity to develop numerous renal cysts

- once kidney 4-6 normal volume, renal fn declines - irreversible damage occurs once GFR decreases - disease progression varies between pts

ADPKD Flashcards by Kathleen McKenzie

PKD

how common
why important

1/1000 live births
most end up on dialysis or kidney transplant
5% end up with ESRD
most common life-threatening inherited renal disease
fourth leading cause of ESRD after DM, HTN, glomerulonephritis

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PKD

- describe

group of monogenic disorders

- characterized by propensity to develop numerous renal cysts

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what is a cyst

fluid filled cavity with no physiological use

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Two main types of PKD

PKD1 (85%) more severe
PKD2 (15%)

*also syndromic forms and autosomal recessive

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What are the proteins coded by PKD1 and PKD2

Polycystin-1 (PC1)
Polycystin-2 (PC2)
membrane proteins, mutation allows for epithelial relaxation which allows formation of cysts

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How else to get PKD other than mutations in PKD1 and 2

de novo mutation

5-10%

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What two essential processes are required for cyst growth?

cell proliferation: size of tubules and cysts increase
fluid secretion: contributes to cyst enlargement
both = cyst growth

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Does cyst location matter?

YES

- inner medullary cyst can potentially diminish urine flow from >16,000 upstream tubules

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What electrolyte is found in the cysts?

Chloride

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Where are cysts found?

only 1 to 3% of nephrons develop cysts

- common collecting ducts

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By how much does kidney volume have to increase to affect kidney function?

4-6 times normal volume

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Progression of PKD

once kidney 4-6 normal volume, renal fn declines
irreversible damage occurs once GFR decreases
disease progression varies between pts

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Renal manifestations of PKD

HTN
renal cysts
hematuria
nocturia
palpable kidneys
kidney stones
abd/flank pain*
renal artery/vein occlusions
recurrent UTIs

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Extrarenal manifestations of PKD

intracranial aneurysms
hepatic cysts (usually worse in women)
pancreatic cysts
hernia
diverticulosis
male infertility

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When to screen for intracranial aneurysm

fam hx
uncontrolled HTN with HA
high risk profession (bus driver, pilot, firefighter)

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DABDA cycle: emotional burden

denial
arguing
bargaining
depression
acceptance

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What must also be assessed after dx of PKC

cardiovascular risk

albumin excretion & LVMI (ACEI)
LDL cholesterol (statin)
smoking (stop)

PKD screening and dx

- family history

confirm autosomal dominant pattern of inheritance

- de novo cases occur too (neg family hx)

PKD screening and dx

- PE

highly variable
sudden onset renal pain or hematuria
HTN
nephromegaly or renal cysts on PE or radiologic exam
microalbuminuria
LVH
pain most common sx
anorexia, nausea, weight loss, pyelonephritis

What dx tool is important for determining how fast cysts are enlarging?

MRI - can measure volume

what is an aquaretic

lose water not electrolytes

PKD screening and dx

- eGFR

best index of kidney function

- 24 hour urine is gold standard but still not 100% accurate

what is the only 100% accurate way to calculate GFR

125I-iothalamate but never used…

PKD screening and dx

- what precedes change in renal function?

changes in kidney volume
- as kidney and cyst volume increase, renal function decreases
(MRI can determine volume)

PKD screening and dx | simple cyst

- cyst wall is fine - cyst liquid is clear *ok to have a few as you age

PKD screening and dx | - diagnosic tests

- US:

US to dx PKD

- confirm dx in setting of positive fam hx - low cost and safe = commonly used - hard to characterize small cysts

Pei criteria for US dx of PKD

- 15-39 yo >= 3 unilateral or bilateral cysts - 40 - 59 yo >=2 bilateral cysts (4 total) - >=60 >= 4 bilateral cysts (8 total)

PKD screening and dx | - when use CT and MRI

- US results equivocal or indeterminate - can detect smaller cysts than US - predictive utility not validated - radiation exposure and dye - MRI is better for soft tissue

Limitations of fam hx and imaging to dx PKD

- may be ambiguous in young pts: renal US may be inconclusive - dx may be challenging if fam hx is unknown - molecular dx methods should be considered

PKD screening and dx | - molecular diagnosis

- DNA linkage analysis: indirect analysis on markers near PKD1 and PKD2 genes - Direct mutation screening: sequencing of PKD1 and PKD2 exons and flanking introns. $$$$

benefits to early dx of PKD

- find living donor - informed family planning - early detection/tx of complications - early preventative therapies (ACEI/ARB) - lifestyle changes to preserve kidney fn

Diagnostic algorithm for PKD

- have fun, in general: - if in doubt of a cyst and pt has fam hx, do an MRI - negative family hx and pt has cysts, do genetic testing

predictors of rapid disease progression

- younger presentation (<50 yo) - GFR 25-30, early decrease - early onset of HTN - gross hematuria - high total kidney volume - PKD1 mutations

Three things to help reduce impact of PKD

- control HTN - ACEI - drink water

ProPKD to assess prognosis in PKD

score <3: progression to ESRD after 60 yo score 3-6: will come earlier than 60 yo score >6: rapid progression, early ESRD

PEARLS: | - what are 3 key factors in PKD dx

- fam hx - age - number and type of cysts

PEARLS: | - what is most common diagnostic tool for dx

- US | - may confirm dx in setting of positive fam hx

PEARLS: | - what two diagnostic tools other than US are used

- MRI and CT - more sensitive than US - can be used to determine total kidney volume which is informative for prognosis

PEARLS: | - what dx tool can be used when have equivocal imaging data and negative fam hx?

molecular (genetic) testing