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Bruce R. Wall, MD, FACP
February 2nd, 2009
 “I
never questioned the integrity of an
umpire… their eyesight, yes…”
Leo Durocher
 “About the only problem with success is that is
does not teach you how to deal with failure”
Tommy Lasorda
 “I think the good Lord is a Yankee”
Mariano Rivera
 “If you come to a fork in the road, take it…”
Yogi Berra
 AD-PCKD
(AR-PCKD)
 Acquired renal cystic disease
 Tuberous sclerosis – angiomyolipoma
 AD-Von Hippel Landau
 Benign
simple cysts – 25% on sonogram;
perhaps 50% males have cyst on CT scan
 Medullary sponge kidney – tubular dilatation
collecting ducts, confined to the medulla
 Bilateral parapelvic cysts – benign
 X linked orofacialdigital syndrome type I
 Multiple
renal cysts
 Forehead plaques
 Hypomelanotic macules
 Retinal hamartoma (nodular)
 Rectal polyps
 Gingival fibromas
 Brain, eyes, heart, liver, kidney, skin, CNS
are affected
 Multiple
renal cyts
 Retinal hemangiomas
 Renal clear cell carcinomas
 CNS hemagioblastomas
 Pheochromocytoma
 Pancreatic cysts
 Epididymal cysts
 Occurring
in 1 in every 400 to 1000 births
 < 50% will be diagnosed (clinically silent)
 Most families abnormal chromosome 16 (called
PKD1 locus)
 Other gene is on chromosome 4 (PKD2 locus)
 PKD1 96% of North America; 85% of Europe
 Both encode proteins aka “polycystin I & II”
 PKD1 gene is adjacent to gene of Tuberous
sclerosis (TSC2), associated with cyst formation
(angiomyolipoma)
 Genotype/phenotype correlation with PKD1 & 2
“unclear” – immense size, complexity, allelic
heterogeneity
 Genomic
duplication of PKD1 “like genes”;
therefore, screening for mutations is difficult
due to large number
Negative Family History may occur in up to 25%
of cases, even with sonogram that is very
suggestive of PCKD
There may be no affected parent (or no
diagnosis in the parent)
Could easily be a new mutation
Ten or more cysts = likely good criteria for DX
 Multi-center
NIH funded study
 ACE vs ACE & ARB medication to slow rate of
loss of function
 Preserved kidney function arm (GFR > 60)
 Advanced kidney disease (30 to 60 ml/min)
 Rumors about use of VAPTINS
 Localized
in renal tubular epithelia, hepatic
ductules, pancreatic ducts (all sites in PCKD)
 Integral membrane protein
 Overexpressed in most cysts in kidney from PCKD
patients
 Cause abnormalities in renal cilia
 May induce cell cycle arrest
 Why is there variable phenotypic expression?
 Defect is present in 100% of cells, yet only 10%
of tubules form cysts… (second hit hypothesis?)
 Therefore – mechanism of cyst formation and
growth is unclear (abnormal differentiation or
cell maturation)
 Easy
diagnosis in overt disease: flank pain,
positive family history, CRI, large kidneys with
multiple bilateral cysts on CT or sonogram
 Cysts in liver, pancreas, and spleen
 What do you do with otherwise unexplained
CRI, hematuria, with negative family history?
 Bilateral
cystic disorder in kidneys with ESRD
from non-cystic disease
 25 to 40% replacement of renal parenchyma
 CT scan or US demonstrating > 5 cysts
 Incidence
in ESRD patients may be > 25%
 Grantham and Levine report 40% incidence
with 6% tumors…
 May occur in any patient with creatinine
above 3mg%
 Geographic incidence is elevated in Japan
 Gross
findings: overall kidney size is smaller
 Mean weight 76gms
 Cysts may be cortex or cortico-medullary
 Usually less than 2-3cms
 Clear fluid, rarely hemorrhagic
 Only
when complicated by hemorrhage or
tumor
 For tumors > 3 cm??
 Symptoms of malignancy
 Part of pre-transplant work up
 ACKD
occurs in ESRD with all causes of renal
failure
 May be common
 Pathogenesis is poorly understood
 Function of total duration on dialysis
 Risk for RCC is elevated
 Screening is controversial