Transcript ppt
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