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