Cystic Kidney Diseases

Question 1

autosomal dominant polycystic kidney disease (ADPKD) - epidemiology

Answer 1

*affects ADULTS
*most common hereditary renal disease
*affects 1/1000 live births
*4th cause of ESRD (about 5% of ESRD population)

Question 2

autosomal dominant polycystic kidney disease (ADPKD) - overview

Answer 2

*expanding cysts that ultimately destroy the renal parenchyma and cause renal failure
*about 50% of pts develop ESRD
*drop in GFR by 3-5 mL/min/year
*rise in serum creatinine after the 4th decade of life

Question 3

autosomal dominant polycystic kidney disease (ADPKD) - genetics

Answer 3

*ADPKD type 1:
-PKD1 gene on chromosome 16
-gene product: polycystin-1
-majority of ADPKD pts
-typically more severe disease due to development of more cysts at an early age
-avg. age ESRD: 55

*ADPKD type 2:
-PKD2 gene on chromosome 4
-gene product: polycystin-2
-avg. age ESRD: 74 (later onset, less severe)

Question 4

distribution of cysts in ADPKD

Answer 4

*renal cysts develop along any portion of the tubule
*direct correlation between rate of cyst growth and renal function decline

Question 5

autosomal dominant polycystic kidney disease (ADPKD) - pathophysiology

Answer 5

*deficits in PKD1/PKD2 → defects in PC-1 or PC-2 → defects in primary cilium (tubular flow sensor) → imbalance in 2 major intracellular messengers, Ca2+ and cAMP
*results in upregulated and downregulated pathways
*there is aberrant transporter location in ADPKD, leading to cyst growth

Question 6

ADPKD - renal complications

Answer 6

*cerebral aneurysms
*HTN
*gross hematuria
*cyst rupture, cyst bleeding
*infection: UTI or cyst infection
*nephrolithiasis
*renal failure
-note: FHx of progression to dialysis associated with increased risk of progression to dialysis

Question 7

ADPKD - diagnosis

Answer 7

*imaging to confirm
*age < 40: 3+ cysts total
*age 40-60: 4+ cysts total
*age > 60: 4 or more cysts in each kidney

Question 8

screening for cerebral aneurysms in patients with ADPKD

Answer 8

*positive FHx of intercranial hemorrhage or cerebral aneurysm
*“warning symptoms” - neuro sx
*high-risk occupation
*upcoming surgery (hemodynamic instability, HTN)
*when needed to start anticoagulation

Question 9

ADPKD - genetic testing

Answer 9

*not generally recommended except for research purposes
*many genes known, but some may have new mutations

Question 10

management of ADPKD

Answer 10

*patient education:
-genetic disease; family members may be afflicted
-complications
-screening
-risk for progression to ESRD

*prognostic factors:
-HTN, early onset sx, male gender
-PKD1 has worse prognosis
-baseline total kidney volume (ultrasound or MRI) and rate of kidney volume growth

Question 11

ADPKD management: BP control

Answer 11

*use RAAS inhibitors (ACEi or ARB)
*aim for more vigorous BP control in younger pts with ADPKD who still have a preserved eGFR

Question 12

ADPKD management - additional management strategies

Answer 12

*increase fluid intake
*early treatment of UTI with cyst-penetrating drugs (TMP-SMX, fluoroquinolone, chloramphenicol)
*cyst management (cyst aspiration with EtOH sclerosis, surgical fenestration, nephrectomy)
*nephrolithiasis management

Question 13

ADPKD management - disease-modifying agent

Answer 13

*vasopressin V2 receptor antagonists [tolvaptan]
*ADEs: polyuria, nocturia, liver failure
*reserved for pts with risk for rapid progression
*exclusions: pregnancy, hypernatremia, liver disease, urinary tract obstructions, concomitant CYP2Ai, caution with diuretics

Question 14

autosomal recessive polycystic kidney disease (ARPKD) - gross pathology

Answer 14

*kidneys retain their reniform shape
*dilated collecting ducts extend through the cortex

Question 15

autosomal recessive polycystic kidney disease (ARPKD) - genetics

Answer 15

*caused by a mutation in PKHD1 gene on chromosome 6
*protein: fibrocystin
*affects NEONATES & CHILDREN

Question 16

autosomal recessive polycystic kidney disease (ARPKD) - cyst distribution

Answer 16

*renal cysts develop solely in the terminal portion of the nephron (COLLECTING DUCTS)

Question 17

autosomal recessive polycystic kidney disease (ARPKD) - clinical presentation

Answer 17

*enlarged kidneys and biliary dysgenesis leading to portal fibrosis/congenital hepatic fibrosis
*high variability in clinical presentation:
-neonatal death (Potter’s phenotype)
-later presentation with minimal kidney disease and s/s of portal HNT
*perinatal mortality: 30-50%
*50% of affected babies who survive the neonatal period progress to ESRD within 10 years

Question 18

autosomal recessive polycystic kidney disease (ARPKD) - diagnosis

Answer 18

*fetal ultrasound at 16 and 20 weeks to evaluate kidneys & amniotic fluid
*milder phenotypes manifest in first few years of life
*genetic testing

Question 19

autosomal recessive polycystic kidney disease (ARPKD) - management

Answer 19

*BP control
*dialysis/transplant
*medical management of portal HTN

Question 20

disorders that can mimic polycystic kidney disease

Answer 20

*tuberous sclerosis
*Von Hippel-Lindau disease
*medullary cystic kidney disease (MCKD)

Question 21

simple kidney cysts

Answer 21

*increasingly common with age
*typically asymptomatic; usually an incidental findings
*on ultrasound: smooth walls, no septae, no intracystic debris
*on CT: homogenous attenuation, no contrast enhancement, thin and smooth walls, usually no calcifications

Question 22

medullary cystic kidney disease (MCKD)

Answer 22

*autosomal dominant disorder that occurs in adults
*mutations in: 1) UMOD gene; 2) REN gene; 3) unidentified gene
*GOUT at early age; polyuria; bland urine sediment
*lack of extrarenal manifestations other than gout
*kidney biopsy: tubulointerstitial fibrosis

Question 23

acquired cystic disease (dialysis associated)

Answer 23

*occurs in kidneys from pt with ESRD who have undergone prolonged dialysis
*complications: rupture, hematuria, RENAL CELL CARCINOMA, polycythemia