Renal Cysts: PCKD & Acquired RENAL cystic disease

1. Renal Cysts: PCKD & Acquired RENAL cystic disease Bruce R. Wall, MD, FACP February 2nd, 2009

2. baseball quotes • “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

3. Renal disease associated with cysts… beyond solitary cyst • 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

4. Medullary sponge kidney

5. Medullary sponge kidney

6. Tuberous sclerosis: neurocutaneous disorder • Multiple renal cysts • Forehead plaques • Hypomelanotic macules • Retinal hamartoma (nodular) • Rectal polyps • Gingival fibromas • Brain, eyes, heart, liver, kidney, skin, CNS are affected

7. Tuberous sclerosis

8. Tuberous sclerosis

9. TS angiofibromas

10. TS hypomelanotic plaque

11. TS forehead plaque

12. AD-von hippel landau • Multiple renal cyts • Retinal hemangiomas • Renal clear cell carcinomas • CNS hemagioblastomas • Pheochromocytoma • Pancreatic cysts • Epididymal cysts

13. Genetics of PCKD: “nice gene” • 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

14. Genetics of PCKD • 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

15. Halt study for PCKD • 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

16. Polycystin 1 • 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)

17. Origin of PCKD…

19. Diagnosis and screening for PCKD • 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?

29. Definition of ACKD • 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

30. EPIdemiology of ackd • 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

31. Pathology of ACKD • 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

32. Ackd: nephrectomy • Only when complicated by hemorrhage or tumor • For tumors > 3 cm?? • Symptoms of malignancy • Part of pre-transplant work up

33. ACKD

34. Complex mass in ACKD

35. RCC in acquired cystic disease

36. Renal Cell Carcinoma

37. conclusion • 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