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 numberNegative 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 mutationTen 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