ADPKD Flashcards
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
PKD
- describe
- group of monogenic disorders
- characterized by propensity to develop numerous renal cysts
what is a cyst
fluid filled cavity with no physiological use
Two main types of PKD
- PKD1 (85%) more severe
- PKD2 (15%)
*also syndromic forms and autosomal recessive
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
How else to get PKD other than mutations in PKD1 and 2
de novo mutation
5-10%
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
Does cyst location matter?
YES
- inner medullary cyst can potentially diminish urine flow from >16,000 upstream tubules
What electrolyte is found in the cysts?
Chloride
Where are cysts found?
- only 1 to 3% of nephrons develop cysts
- common collecting ducts
By how much does kidney volume have to increase to affect kidney function?
4-6 times normal volume
Progression of PKD
- once kidney 4-6 normal volume, renal fn declines
- irreversible damage occurs once GFR decreases
- disease progression varies between pts
Renal manifestations of PKD
- HTN
- renal cysts
- hematuria
- nocturia
- palpable kidneys
- kidney stones
- abd/flank pain*
- renal artery/vein occlusions
- recurrent UTIs
Extrarenal manifestations of PKD
- intracranial aneurysms
- hepatic cysts (usually worse in women)
- pancreatic cysts
- hernia
- diverticulosis
- male infertility
When to screen for intracranial aneurysm
- fam hx
- uncontrolled HTN with HA
- high risk profession (bus driver, pilot, firefighter)
DABDA cycle: emotional burden
- denial
- arguing
- bargaining
- depression
- acceptance
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
