Renal Cystic Disorders Nadeem A Siddiqui MD. Renal cystic disorders Non-genetic Non-genetic A) Developmental: Medullary sponge kidney Renal cystic dysplasia.

Renal Cystic DisordersRenal Cystic Disorders

Nadeem A Siddiqui MDNadeem A Siddiqui MD

Renal cystic disordersRenal cystic disorders Non-geneticNon-genetic

A) Developmental:A) Developmental:

Medullary sponge kidneyMedullary sponge kidney

Renal cystic dysplasiaRenal cystic dysplasia

B)Acquired:B)Acquired:

Simple cystsSimple cysts

Hypokalemia relatedHypokalemia related

CKD relatedCKD related

Renal LymphangiomatosisRenal Lymphangiomatosis

Solitary Multilocular cystsSolitary Multilocular cysts

Renal cystic disordersRenal cystic disorders

Genetic: ADGenetic: AD

ADPKDADPKD

Von Hipple-LindauVon Hipple-Lindau

Tuberous SclerosisTuberous Sclerosis

Medullary cystic Medullary cystic diseasedisease

Genetic: ARGenetic: AR

ARPKDARPKD

Juvenile Juvenile nephronophthisisnephronophthisis

X Linked:X Linked:

Orofacial digital Orofacial digital syndrome type 1syndrome type 1

ADPKD: EpidemiologyADPKD: Epidemiology

Incidence 1:400 to 1:1000Incidence 1:400 to 1:1000 Current number affected:400,000Current number affected:400,000 Approximately 1800 started on HD Approximately 1800 started on HD

each yeareach year Racial distributionRacial distribution

GeneticsGenetics

PKD1…..85 to 90 % PKD1…..85 to 90 % PKD2…..10 to 15 %PKD2…..10 to 15 % PKD1 gene is on 16p and codes for PKD1 gene is on 16p and codes for

polycystin 1. It has 3 homologous polycystin 1. It has 3 homologous copies and hence mutations are copies and hence mutations are difficult to identifydifficult to identify

PKD2 gene is located on 4p and PKD2 gene is located on 4p and codes for polycystin 2codes for polycystin 2

GeneticsGenetics

Both polycystin 1 and 2 are Both polycystin 1 and 2 are regulatory proteins involved in regulatory proteins involved in regulation of ion channels. PKD2 may regulation of ion channels. PKD2 may regulate calcium channel functionregulate calcium channel function

ADPKD kidneys stain heavily for ADPKD kidneys stain heavily for polycystinspolycystins

Clinical FeaturesClinical Features

RenalRenal

1.Hematuria1.Hematuria

2.Infection2.Infection

3.Nephrolithiasis3.Nephrolithiasis

4.Hypertension4.Hypertension

5.Renal failure5.Renal failure

6.Pain6.Pain

7.Cyst rupture and torsion7.Cyst rupture and torsion

8.Functional renal disease8.Functional renal disease

Extra RenalExtra Renal

1.Polycystic liver disease1.Polycystic liver disease

2.Intracranial Aneurysms2.Intracranial Aneurysms

3.Valvular heart disease3.Valvular heart disease

HypertensionHypertension

Seen in 60 to 100% of patientsSeen in 60 to 100% of patients

Gross HematuriaGross Hematuria

Seen in up to 50% of patientsSeen in up to 50% of patients Flank painFlank pain Cyst hemorrhage may occur in the Cyst hemorrhage may occur in the

absence of gross hematuriaabsence of gross hematuria Cyst rupture can cause retro-Cyst rupture can cause retro-

peritoneal bleedingperitoneal bleeding

Cyst InfectionCyst Infection

UTIUTI PyelonephritisPyelonephritis Perinephric abscessPerinephric abscess

NephrolithiasisNephrolithiasis

Seen in up to 25% of all ADPKD patientsSeen in up to 25% of all ADPKD patients Stones contain uric acid and calcium Stones contain uric acid and calcium

oxalate oxalate Factors responsible for Factors responsible for

nephrolithogenesis nephrolithogenesis

include decreased urinary include decreased urinary NH4,decreased urinary PH , and NH4,decreased urinary PH , and decreased urinary citratedecreased urinary citrate

Renal functional ImpairmentRenal functional Impairment

Renal concentration defectRenal concentration defect Decreased renal blood flowDecreased renal blood flow Acidification defect ( decreased NH3)Acidification defect ( decreased NH3) Increase in renal Angiotensin activity Increase in renal Angiotensin activity

and matrix synthesisand matrix synthesis

Renal FailureRenal Failure

Seen in 50% of patients by age 60Seen in 50% of patients by age 60

ESRD in ADPKDESRD in ADPKD

16,298 patients were treated for 16,298 patients were treated for ADPKD (5% of all ESRD)ADPKD (5% of all ESRD)

2,144 patients entered ESRD2,144 patients entered ESRD 50% of all ADPKD patients enter 50% of all ADPKD patients enter

ESRD by age 60ESRD by age 60 Total cost of RRT for ADPKD pts Total cost of RRT for ADPKD pts

exceeded $1 billion exceeded $1 billion Data from FY 2000Data from FY 2000

Risk factors for rapid loss of Risk factors for rapid loss of renal functionrenal function

HypertensionHypertension Gross HematuriaGross Hematuria UTIUTI MultiparityMultiparity Male sexMale sex Black raceBlack race

Dx of ADPKD Dx of ADPKD before age 30before age 30

Onset of hematuria Onset of hematuria before age 30before age 30

DyslipidemiaDyslipidemia DD ACE DD ACE

polymorphismpolymorphism Sickle cell diseaseSickle cell disease

Extra-renal disease: PLDExtra-renal disease: PLD

Dx: > 4 cysts in the liverDx: > 4 cysts in the liver May occur independent of PKDMay occur independent of PKD Biliary hamartomas, biliary fibroadenomas, Biliary hamartomas, biliary fibroadenomas,

dilatation of intra/extra hepatic ductsdilatation of intra/extra hepatic ducts Liver cysts increase with estrogen exposureLiver cysts increase with estrogen exposure Cysts may cause abdominal distension, Cysts may cause abdominal distension,

dyspnea, obstructive jaundice and ascites dyspnea, obstructive jaundice and ascites due to IVC compressiondue to IVC compression

Extra-renal disease: ICAExtra-renal disease: ICA

Overall incidence 8% of all ADPKD patientsOverall incidence 8% of all ADPKD patients Familial clustering ( 22% of those with Familial clustering ( 22% of those with

familial h/o ICA)familial h/o ICA) Majority are asymptomaticMajority are asymptomatic Yearly rupture rate is 0.5% for aneurysms Yearly rupture rate is 0.5% for aneurysms

<5 mm and 4% for aneurysms >10 mm <5 mm and 4% for aneurysms >10 mm 1/3 of all patients with a ruptured aneurysm 1/3 of all patients with a ruptured aneurysm

are not hypertensive at the time of ruptureare not hypertensive at the time of rupture

Indications for screening for Indications for screening for ICAICA

Family h/o ICA/SAHFamily h/o ICA/SAH Prior aneurysmal rupturePrior aneurysmal rupture Before high risk surgeryBefore high risk surgery High risk occupationHigh risk occupation Anxiety on part of the patientAnxiety on part of the patient

Screening for ICAScreening for ICA

MRA with gadolinium is highly MRA with gadolinium is highly sensitive and does not impose risk of sensitive and does not impose risk of contrast nephropathycontrast nephropathy

Extra-renal disease: Valvular Extra-renal disease: Valvular heart diseaseheart disease

MVP….25%MVP….25% MR,TR, tricuspid valve prolapse, AI .MR,TR, tricuspid valve prolapse, AI . Histopathology: myxoid degenerationHistopathology: myxoid degeneration Screening: if clinically indicatedScreening: if clinically indicated

Diagnostic testingDiagnostic testing

Ultrasound diagnosisUltrasound diagnosis Genetic diagnosisGenetic diagnosis Pre-symptomatic diagnosisPre-symptomatic diagnosis

Diagnostic Criteria- Diagnostic Criteria- UltrasoundUltrasound

Age 15-29 ………..2 cysts in one or both kidneysAge 15-29 ………..2 cysts in one or both kidneys Age 30 to 59 …….2 cysts in each kidneyAge 30 to 59 …….2 cysts in each kidney Age >60 ………….4 cysts in each kidneyAge >60 ………….4 cysts in each kidney

Case # 1Case # 1

A 32 year old man with known h/o A 32 year old man with known h/o ADPKD comes to your clinic with a ADPKD comes to your clinic with a two day h/o left flank pain.two day h/o left flank pain.

BP160/90, temp 98.4. BP160/90, temp 98.4. left kidney is palpable and tenderleft kidney is palpable and tender Serum creatinine is 1.0 and UA Serum creatinine is 1.0 and UA

shows microscopic hematuria. Urine shows microscopic hematuria. Urine gram stain is negativegram stain is negative

Case #1 continuedCase #1 continued

Which diagnostic test would be Which diagnostic test would be most appropriate:most appropriate:

1)1) Excretory UrographyExcretory Urography

2)2) USGUSG

3)3) CT with and without Contrast CT with and without Contrast

4)4) MRIMRI

ADPKD genetic diagnosisADPKD genetic diagnosis

PKD2 100% mutations detectablePKD2 100% mutations detectable PKD1 75 to 80% mutations PKD1 75 to 80% mutations

detectabledetectable

Genetic screening Genetic screening

Who should be screened:Who should be screened:

Equivocal sonogram in a young adult Equivocal sonogram in a young adult who is a potential renal transplant who is a potential renal transplant donordonor

Issues :Issues :

Psychological burdenPsychological burden

Insurance and employment riskInsurance and employment risk

Rx of ADPKDRx of ADPKD

Treatment of Flank pain: Treatment of Flank pain:

AnalgesicsAnalgesics

Avoid NSAIDSAvoid NSAIDS

Risk of narcotic dependence Risk of narcotic dependence

Cyst decompression, aspiration, ethanolCyst decompression, aspiration, ethanol

sclerosis and laparoscopic fenestration sclerosis and laparoscopic fenestration

Rx of ADPKDRx of ADPKD

Treatment of Cyst hemorrhageTreatment of Cyst hemorrhage

Self limitedSelf limited

Segmental artery embolizationSegmental artery embolization

Rx of ADPKDRx of ADPKD

Cyst InfectionCyst Infection

BactrimBactrim

QuinolonesQuinolones

ChloremphnicolChloremphnicol

Rx of ADPKDRx of ADPKD

Nephrolithiasis:Nephrolithiasis:

Extracorporeal shock wave Extracorporeal shock wave lithotripsylithotripsy

Potassium citrate / Bicitra for Potassium citrate / Bicitra for prevention of nephrolithiasis if prevention of nephrolithiasis if neededneeded

Rx of ADPKDRx of ADPKD

Hypertension:Hypertension:

ACE Inhibitors and ARB are preferred ACE Inhibitors and ARB are preferred

Rx of ADPKDRx of ADPKD

Treatment of CKDTreatment of CKD

Dietary protein restrictionDietary protein restriction

Control of dyslipidemia ( statins)Control of dyslipidemia ( statins)

Control of acidosisControl of acidosis

Prevention of hyperphosphatemiaPrevention of hyperphosphatemia

management of hypertensionmanagement of hypertension

ARPKDARPKD

Incidence 1:20,000Incidence 1:20,000 30% effected 30% effected

neonates die neonates die Genetic locus: 6pGenetic locus: 6p

Clinical features:Clinical features:

OligohydramniosOligohydramnios

Large echogenic Large echogenic kidneyskidneys

Pulmonary hypoplasiaPulmonary hypoplasia

HematuriaHematuria

PyuriaPyuria

Systemic hypertensionSystemic hypertension

Portal HypertensionPortal Hypertension

Case #2Case #2

49 yr old female 49 yr old female presents with presents with biliary colic. biliary colic.

H/o petit mal H/o petit mal seizures in her son seizures in her son and h/o hypo and h/o hypo pigmented pigmented macules in her macules in her grandsongrandson

Physical exam: Physical exam: scattered flesh scattered flesh colored facial colored facial papules, two dental papules, two dental enamel pits, and enamel pits, and many scattered many scattered hypo pigmented hypo pigmented maculesmacules

Case #2 continued Case #2 continued

Labs: normal chemistries and blood Labs: normal chemistries and blood count and normal serum creatininecount and normal serum creatinine

CT of the abdomen: Contrast CT of the abdomen: Contrast enhancing masses in enhancing masses in both both kidneyskidneys

Tuberous Sclerosis Complex Tuberous Sclerosis Complex (TSC)(TSC)

ADAD Prevalence 1:10,000Prevalence 1:10,000 Genetic loci: Genetic loci:

TSC1…9qTSC1…9q

TSC2…16p adjacentTSC2…16p adjacent

to PKD1 locus to PKD1 locus Gene product is Tuberin (GTP ase) Gene product is Tuberin (GTP ase)

TSC: Clinical featuresTSC: Clinical features

Renal cysts and Renal cysts and angiomyolipomasangiomyolipomas

Renal cell Renal cell carcinoma carcinoma (bilateral)(bilateral)

Cortical tuberCortical tuber Retinal hamartomaRetinal hamartoma GliomaGlioma AstrocytomaAstrocytoma

Facial angiofibromaFacial angiofibroma Ungual fibromaUngual fibroma Shagreen patchShagreen patch Cardiac Cardiac

rhabdomyomarhabdomyoma Pulmonary Pulmonary

lymphangioleiomyolymphangioleiomyomama

Thyroid adenomaThyroid adenoma

von Hippel-Lindau (VHL)von Hippel-Lindau (VHL)

Prevalence 1:30,000Prevalence 1:30,000 VHL1 : VHL1 :

1. Retinal Angioma1. Retinal Angioma

2. Spinal/ cerebellar 2. Spinal/ cerebellar hemangioblastoma hemangioblastoma

3. Pancreatic and 3. Pancreatic and renal cystsrenal cysts

4.Renal cell cancer 4.Renal cell cancer

VHL2: as in VHL1 VHL2: as in VHL1 +Pheochromocyto+Pheochromocytoma ma