Renal Cystic Disorders

1. Renal Cystic Disorders Nadeem A Siddiqui MD

2. Renal cystic disorders • Non-genetic A) Developmental: Medullary sponge kidney Renal cystic dysplasia B)Acquired: Simple cysts Hypokalemia related CKD related Renal Lymphangiomatosis Solitary Multilocular cysts

3. Genetic: AD ADPKD Von Hipple-Lindau Tuberous Sclerosis Medullary cystic disease Genetic: AR ARPKD Juvenile nephronophthisis X Linked: Orofacial digital syndrome type 1 Renal cystic disorders

4. ADPKD: Epidemiology • Incidence 1:400 to 1:1000 • Current number affected:400,000 • Approximately 1800 started on HD each year • Racial distribution

5. Genetics • PKD1…..85 to 90 % • PKD2…..10 to 15 % • PKD1 gene is on 16p and codes for polycystin 1. It has 3 homologous copies and hence mutations are difficult to identify • PKD2 gene is located on 4p and codes for polycystin 2

6. Genetics • Both polycystin 1 and 2 are regulatory proteins involved in regulation of ion channels. PKD2 may regulate calcium channel function • ADPKD kidneys stain heavily for polycystins

7. Renal 1.Hematuria 2.Infection 3.Nephrolithiasis 4.Hypertension 5.Renal failure 6.Pain 7.Cyst rupture and torsion 8.Functional renal disease Extra Renal 1.Polycystic liver disease 2.Intracranial Aneurysms 3.Valvular heart disease Clinical Features

8. Hypertension • Seen in 60 to 100% of patients

9. Gross Hematuria • Seen in up to 50% of patients • Flank pain • Cyst hemorrhage may occur in the absence of gross hematuria • Cyst rupture can cause retro-peritoneal bleeding

10. Cyst Infection • UTI • Pyelonephritis • Perinephric abscess

11. Nephrolithiasis • Seen in up to 25% of all ADPKD patients • Stones contain uric acid and calcium oxalate • Factors responsible for nephrolithogenesis include decreased urinary NH4,decreased urinary PH , and decreased urinary citrate

12. Renal functional Impairment • Renal concentration defect • Decreased renal blood flow • Acidification defect ( decreased NH3) • Increase in renal Angiotensin activity and matrix synthesis

13. Renal Failure • Seen in 50% of patients by age 60

14. ESRD in ADPKD • 16,298 patients were treated for ADPKD (5% of all ESRD) • 2,144 patients entered ESRD • 50% of all ADPKD patients enter ESRD by age 60 • Total cost of RRT for ADPKD pts exceeded $1 billion Data from FY 2000

15. Hypertension Gross Hematuria UTI Multiparity Male sex Black race Dx of ADPKD before age 30 Onset of hematuria before age 30 Dyslipidemia DD ACE polymorphism Sickle cell disease Risk factors for rapid loss of renal function

16. Extra-renal disease: PLD • Dx: > 4 cysts in the liver • May occur independent of PKD • Biliary hamartomas, biliary fibroadenomas, dilatation of intra/extra hepatic ducts • Liver cysts increase with estrogen exposure • Cysts may cause abdominal distension, dyspnea, obstructive jaundice and ascites due to IVC compression

17. Extra-renal disease: ICA • Overall incidence 8% of all ADPKD patients • Familial clustering ( 22% of those with familial h/o ICA) • Majority are asymptomatic • Yearly rupture rate is 0.5% for aneurysms <5 mm and 4% for aneurysms >10 mm • 1/3 of all patients with a ruptured aneurysm are not hypertensive at the time of rupture

18. Indications for screening for ICA • Family h/o ICA/SAH • Prior aneurysmal rupture • Before high risk surgery • High risk occupation • Anxiety on part of the patient

19. Screening for ICA • MRA with gadolinium is highly sensitive and does not impose risk of contrast nephropathy

20. Extra-renal disease: Valvular heart disease • MVP….25% • MR,TR, tricuspid valve prolapse, AI . • Histopathology: myxoid degeneration • Screening: if clinically indicated

21. Diagnostic testing • Ultrasound diagnosis • Genetic diagnosis • Pre-symptomatic diagnosis

22. Diagnostic Criteria- Ultrasound Age 15-29 ………..2 cysts in one or both kidneys Age 30 to 59 …….2 cysts in each kidney Age >60 ………….4 cysts in each kidney

23. Case # 1 • A 32 year old man with known h/o ADPKD comes to your clinic with a two day h/o left flank pain. • BP160/90, temp 98.4. left kidney is palpable and tender • Serum creatinine is 1.0 and UA shows microscopic hematuria. Urine gram stain is negative

24. Case #1 continued • Which diagnostic test would be most appropriate: • Excretory Urography • USG • CT with and without Contrast • MRI

25. ADPKD genetic diagnosis • PKD2 100% mutations detectable • PKD1 75 to 80% mutations detectable

26. Genetic screening Who should be screened: Equivocal sonogram in a young adult who is a potential renal transplant donor Issues : Psychological burden Insurance and employment risk

27. Rx of ADPKD • Treatment of Flank pain: Analgesics Avoid NSAIDS Risk of narcotic dependence Cyst decompression, aspiration, ethanol sclerosis and laparoscopic fenestration

28. Rx of ADPKD • Treatment of Cyst hemorrhage Self limited Segmental artery embolization

29. Rx of ADPKD • Cyst Infection Bactrim Quinolones Chloremphnicol

30. Rx of ADPKD • Nephrolithiasis: Extracorporeal shock wave lithotripsy Potassium citrate / Bicitra for prevention of nephrolithiasis if needed

31. Rx of ADPKD • Hypertension: ACE Inhibitors and ARB are preferred

32. Rx of ADPKD • Treatment of CKD Dietary protein restriction Control of dyslipidemia ( statins) Control of acidosis Prevention of hyperphosphatemia management of hypertension

33. Incidence 1:20,000 30% effected neonates die Genetic locus: 6p Clinical features: Oligohydramnios Large echogenic kidneys Pulmonary hypoplasia Hematuria Pyuria Systemic hypertension Portal Hypertension ARPKD

34. 49 yr old female presents with biliary colic. H/o petit mal seizures in her son and h/o hypo pigmented macules in her grandson Physical exam: scattered flesh colored facial papules, two dental enamel pits, and many scattered hypo pigmented macules Case #2

35. Case #2 continued • Labs: normal chemistries and blood count and normal serum creatinine • CT of the abdomen: Contrast enhancing masses in both kidneys

36. Tuberous Sclerosis Complex (TSC) • AD • Prevalence 1:10,000 • Genetic loci: TSC1…9q TSC2…16p adjacent to PKD1 locus • Gene product is Tuberin (GTP ase)

37. Renal cysts and angiomyolipomas Renal cell carcinoma (bilateral) Cortical tuber Retinal hamartoma Glioma Astrocytoma Facial angiofibroma Ungual fibroma Shagreen patch Cardiac rhabdomyoma Pulmonary lymphangioleiomyoma Thyroid adenoma TSC: Clinical features

38. Prevalence 1:30,000 VHL1 : 1. Retinal Angioma 2. Spinal/ cerebellar hemangioblastoma 3. Pancreatic and renal cysts 4.Renal cell cancer VHL2: as in VHL1 +Pheochromocytoma von Hippel-Lindau (VHL)