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Cystic Diseases of the Cystic Diseases of the
KidneyKidney
Derek OttemDerek Ottem
UGR May 30UGR May 30thth 20072007
OverviewOverview
Classification of Renal Cystic DiseaseClassification of Renal Cystic Disease
Cyst HistologyCyst Histology
ADPKDADPKD
Acquired Renal Cystic DiseaseAcquired Renal Cystic Disease
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VHL
Tuberous sclerosis
Medullary cystic disease
Simple CystsJuvenile nephronophthesis
Multicystic dysplastic kidney / MCDKJuvenile nephronophthesis–medullary cystic
disease complex
Medullary sponge kidneyFamilial hypoplastic glomerulocystic disease
Calyceal diverticulum / Pyelogenic
cyst
Congenital nephrosis/Familial Nephrotic
Syndrome
Benign multilocular cyst / Cystic
nephroma
ARPKD (infantile)
Acquired renal cystic diseaseADPKD (adult)
Non-GeneticGenetic
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What is a cyst?What is a cyst?
Kidney most common organ to form cystsKidney most common organ to form cysts
Microscopic or macroscopic sacs lined Microscopic or macroscopic sacs lined
with epitheliumwith epithelium
Dilated duct reaches > 4 times itDilated duct reaches > 4 times it’’s normal s normal
diameter (Gardner 1988)diameter (Gardner 1988)
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ADPKDADPKD
EpidemiologyEpidemiology
Genetics and PathogenesisGenetics and Pathogenesis
Screening IssuesScreening Issues
DiagnosisDiagnosis
ManifestationsManifestations
Complications and ManagementComplications and Management
Transplant IssuesTransplant Issues
ADPKD: EpidemiologyADPKD: Epidemiology
1 in 5001 in 500--10001000
Most prevalent monogenic disorderMost prevalent monogenic disorder
Most identified clinically between age 30Most identified clinically between age 30--5050
Age at diagnosis decreasing as genetic testing Age at diagnosis decreasing as genetic testing
becomes more prevalentbecomes more prevalent
Slightly more progressive disease in menSlightly more progressive disease in men
Accounts for 3Accounts for 3--15% of pt15% of pt’’s on RRTs on RRT
Accounts for 3Accounts for 3--13% of renal transplants13% of renal transplants
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ADPKD: GeneticsADPKD: Genetics
PKD1PKD1
Short arm chromosome 16Short arm chromosome 16
16p13.316p13.3
85% of cases of ADPKD85% of cases of ADPKD
Earlier onset and faster progressionEarlier onset and faster progression
Polycystin1 glycoproteinPolycystin1 glycoprotein
Membrane protein receptorMembrane protein receptor
Located in primary ciliumLocated in primary cilium
Average life expectancy 53 yearsAverage life expectancy 53 years
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PKD2PKD2
Chromosome 4Chromosome 4
4q214q21
15% of cases15% of cases
Slower progression and later onsetSlower progression and later onset
Polycystin 2 glycoproteinPolycystin 2 glycoprotein
Membrane proteinMembrane protein
Primary cilium Ca channelPrimary cilium Ca channel
Average life expectancy 69 yearsAverage life expectancy 69 years
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ADPKD: Genetic ImprintingADPKD: Genetic Imprinting
Disease more severe and manifests Disease more severe and manifests
earlier when transmitted from motherearlier when transmitted from mother
ADPKD: Genetic AnticipationADPKD: Genetic Anticipation
Subsequent generations have earlier Subsequent generations have earlier
onset and severity of diseaseonset and severity of disease
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ADPKD: Inter and IntraADPKD: Inter and Intra--Familial Familial
VariabilityVariability
Variability in location of mutationVariability in location of mutation
2 hit phenomenon2 hit phenomenon
Genetic and environmental modifiersGenetic and environmental modifiers
ADPKD: HistologyADPKD: Histology
Cysts range from few mm to several cmCysts range from few mm to several cm
Diffusely throughout cortex and medullaDiffusely throughout cortex and medulla
May resemble portion of nephron from May resemble portion of nephron from
which derivedwhich derived
Epithelial hyperplasia is commonEpithelial hyperplasia is common
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ADPKD: Epithelial HyperplasiaADPKD: Epithelial Hyperplasia
No increased risk of RCCNo increased risk of RCC
Other conditions with epithelial Other conditions with epithelial
hyperplasiahyperplasia
1.1. ARCD (3ARCD (3--6 times population risk)6 times population risk)
2.2. VHL (40VHL (40--50% of VHL pt50% of VHL pt’’s)s)
3.3. TS (2% of TS ptTS (2% of TS pt’’s)s)
Screening for ADPKDScreening for ADPKD
ImagingImaging�� U/S 1U/S 1stst line testline test
Genetic testingGenetic testing�� Linkage AnalysisLinkage Analysis
�� Direct DNA sequencingDirect DNA sequencing
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Benefits of Testing for ADPKDBenefits of Testing for ADPKD
Identification of possible kidney donors Identification of possible kidney donors
Family planningFamily planning
Early detection of disease complicationsEarly detection of disease complications
Early treatment of disease complicationsEarly treatment of disease complications
Detriments of ScreeningDetriments of Screening
PsychologicalPsychological
Educational and career implicationsEducational and career implications
InsurabilityInsurability
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ScreeningScreening
Until effective treatments become Until effective treatments become
available the adverse effects from preavailable the adverse effects from pre--
symtomatic diagnosis in children symtomatic diagnosis in children
outweights the benefitsoutweights the benefits
Lancet April 2007: Torres et al
U/S Diagnosis For 50% At RiskU/S Diagnosis For 50% At Risk
4 cysts in each kidney4 cysts in each kidney>60>60
2 cysts in each kidney2 cysts in each kidney3030--6060
2 unilateral cysts or bilateral cysts (1 cyst each kidney)2 unilateral cysts or bilateral cysts (1 cyst each kidney)<30 <30
CriteriaCriteriaAge Age
*Sensitivity 100% for PKD1 and 67% for PKD2 when <30
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Normal U/S Values per AgeNormal U/S Values per Age
9%9%22.1%22.1%>70>70
4%4%11.5%11.5%5050--7070
1%1%1.7%1.7%3030--5050
<1%<1%<1%<1%1515--3030
Bilateral CystBilateral CystUnilateral CystUnilateral CystAgeAge
Am J Kidney Disease 1993: Ravine et al
Sensitivity of US for ADPKDSensitivity of US for ADPKD
100100100100100100SpecificitySpecificity
979790909898SensitivitySensitivity
Any AgeAny Age
100100100100100100SpecificitySpecificity
100100100100100100SensitivitySensitivity
>30>30
100100100100100100SpecificitySpecificity
939367679595SensitivitySensitivity
<30<30
ADPKDADPKDPKD2PKD2PKD1PKD1AgeAge
Radiology OCT 1999: Nicolau et al
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Diagnosis in Absence of Family Diagnosis in Absence of Family
HistoryHistory
Bilateral Renal Cysts And 2 or more of:Bilateral Renal Cysts And 2 or more of:
1.1. Bilateral renal enlargementBilateral renal enlargement
2.2. 3 or more hepatic cysts3 or more hepatic cysts
3.3. Cerebral artery aneurysmCerebral artery aneurysm
4.4. Arachnoid cystArachnoid cyst
5.5. Pineal gland cystPineal gland cyst
6.6. Pacreatic cystPacreatic cyst
7.7. Splenic cystSplenic cyst
Genetic Testing: LinkageGenetic Testing: Linkage
PKD1 and PKD2 genesPKD1 and PKD2 genes
Linkage analysisLinkage analysis
Blood samples from pt and at least 2 Blood samples from pt and at least 2
affected family members and 2 non affected family members and 2 non
affected family membersaffected family members
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Genetic Testing: Direct DNAGenetic Testing: Direct DNA
Athena DiagnosticsAthena Diagnostics
PKDxPKDx
i.i. Direct DNA test (not linkage Direct DNA test (not linkage –– no family no family
members required)members required)
ii.ii. Detects most PKD1 and PKD2 defectsDetects most PKD1 and PKD2 defects
Potential Indications for Genetic Potential Indications for Genetic
TestingTesting
1.1. Living donor evaluationLiving donor evaluation
2.2. Unclear clinical diagnosisUnclear clinical diagnosis
3.3. Typical presentation without family Typical presentation without family
historyhistory
4.4. Differentiate between PKD1 and PKD2Differentiate between PKD1 and PKD2
5.5. PrePre--natal diagnosisnatal diagnosis
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ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
ADPKD: HTNADPKD: HTN
55--40% of children with ADPKD40% of children with ADPKD
50% of 2050% of 20--35 and normal RF35 and normal RF
100% of pt100% of pt’’s with ESRDs with ESRD
Principle form of presentationPrinciple form of presentation
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HTN: EtiologyHTN: Etiology
Association with renal sizeAssociation with renal size
Stretching of vesselsStretching of vessels
Distal ischemiaDistal ischemia
Activation of RASActivation of RAS
AtherosclerosisAtherosclerosis
PKD1 and 2 found in vessel wallsPKD1 and 2 found in vessel walls
Impaired NO mediated vasodilation in vascular Impaired NO mediated vasodilation in vascular smooth musclesmooth muscle
Insulin resistanceInsulin resistance
HTN: AssociationsHTN: Associations
Reduced renal BFReduced renal BF
Abnormal sodium handlingAbnormal sodium handling
Remodeling of renal vasculatureRemodeling of renal vasculature
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HTN: ComplicationsHTN: Complications
Left ventricular hypertrophyLeft ventricular hypertrophy
Diastolic dysfunctionDiastolic dysfunction
Worsening of MVPWorsening of MVP
Worsening of aneurysmsWorsening of aneurysms
HematuriaHematuria
Major risk factor for IHD / MIMajor risk factor for IHD / MI
Worsening of proteinuria / CRFWorsening of proteinuria / CRF
Increased risk of preIncreased risk of pre--eclampsia / fetal losseclampsia / fetal loss
Effect of Antihypertensive Therapy on Renal Function and UrinaryEffect of Antihypertensive Therapy on Renal Function and Urinary Albumin Excretion in Albumin Excretion in
Hypertensive Patients With Autosomal Dominant Polycystic Kidney Hypertensive Patients With Autosomal Dominant Polycystic Kidney DiseaseDisease
American Journal of Kidney DiseasesAmerican Journal of Kidney Diseases -- Volume 35, Issue 3 (March 2000) Volume 35, Issue 3 (March 2000) -- Copyright Copyright ©© 2000 W. 2000 W.
B. Saunders B. Saunders
RCT Comparing enalapril (ACEI) to RCT Comparing enalapril (ACEI) to
Amlodipine for BP control, Cr and Amlodipine for BP control, Cr and
ProteiuriaProteiuria
ADPKD with CCL <50cc/minADPKD with CCL <50cc/min
No difference in BP or CrNo difference in BP or Cr
ACEI had significantly lower proteinuria at ACEI had significantly lower proteinuria at
1 and 5 years1 and 5 years
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HTN: TreatmentHTN: Treatment
Early detection important Early detection important –– ambulatory BP ambulatory BP
monitoringmonitoring
ACEI better than CCB / HCTZ at reducing ACEI better than CCB / HCTZ at reducing
progression of proteiuria, but no effect on progression of proteiuria, but no effect on
CrCr
Optimal BP unclear, likely <130/80Optimal BP unclear, likely <130/80
HALTHALT--PKD trial PKD trial –– ACEI vs ACEI + ARBACEI vs ACEI + ARB
HALTHALT--PKD PKD –– is 110/75 better than 130/80is 110/75 better than 130/80
ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
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Pain Pain
Most common symptomMost common symptom
Etiology:Etiology:
1.1. InfectionInfection
2.2. Stones / Renal coliStones / Renal coli
3.3. Bleeding into cystBleeding into cyst
4.4. Clot colicClot colic
5.5. Pressure on capsule / adjacent organsPressure on capsule / adjacent organs
6.6. GI (Heartburn)GI (Heartburn)
7.7. DiverticulitisDiverticulitis
8.8. PancreatitisPancreatitis
Pain:TreatmentPain:Treatment
•• Treat identifiable causes (calculi, infections)Treat identifiable causes (calculi, infections)
•• AnalgesicsAnalgesics
•• Percutaneous cyst aspiration and sclerosantPercutaneous cyst aspiration and sclerosant
•• Transcatheter arterial embolizationTranscatheter arterial embolization
•• MIS or Open Cyst UnMIS or Open Cyst Un--roofingroofing
•• MIS Denervation and NephropexyMIS Denervation and Nephropexy
•• MIS or Open NephrectomyMIS or Open Nephrectomy
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Pilot study of 15 pts over 1 year periodPilot study of 15 pts over 1 year period
Percutaneous cyst aspiration and injection of Percutaneous cyst aspiration and injection of
99% ETOH99% ETOH
Selected cysts were >5cm + pressure signs on Selected cysts were >5cm + pressure signs on
IVU or CECTIVU or CECT
Visual analog pain score, Cr and serial imagingVisual analog pain score, Cr and serial imaging
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ETOH Injection: ResultsETOH Injection: Results
Pain scores improved at 1 day and 1 Pain scores improved at 1 day and 1
monthmonth
Cr significantly increased at 1 year Cr significantly increased at 1 year
1.9mg/dL to 2.1mg/dL1.9mg/dL to 2.1mg/dL
Complications in 2 of 15 ptComplications in 2 of 15 pt’’ss
1 Pt developed nephrocutaneous fistula1 Pt developed nephrocutaneous fistula
1Pt developed UTI1Pt developed UTI
1.1. Absolute ETOHAbsolute ETOH
2.2. NN--ButylButyl--CyanoacrylateCyanoacrylate
3.3. EthanolamineEthanolamine
4.4. Povidone iodinePovidone iodine
5.5. Acetic acidAcetic acid
6.6. DextroseDextrose
7.7. Tetracycline, MinocyclineTetracycline, Minocycline
8.8. PhenolPhenol
9.9. BismuthBismuth
10.10. Fibrin glueFibrin glue
11.11. GlucoseGlucose
Sclerosing AgentsSclerosing Agents
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Cyst Unroofing:HistoricalCyst Unroofing:Historical
1911 1911 –– Rovsing unroofed cysts surgically Rovsing unroofed cysts surgically
in 3 patients to relieve painin 3 patients to relieve pain
Deteriorating renal function Deteriorating renal function -- procedure procedure
lost enthusiasmlost enthusiasm
1951 Goldstein (16 pts ) and Dalgaard 1951 Goldstein (16 pts ) and Dalgaard
(199 pts) (199 pts) -- significant pain reflief with cyst significant pain reflief with cyst
decorticationdecortication
Cyst Unroofing:HistoricalCyst Unroofing:Historical
1957 Bricker 1957 Bricker –– NEJM NEJM –– 2 patients had 2 patients had
worsening renal function after cyst worsening renal function after cyst
decortication for paindecortication for pain
Procedure discredited for 20Procedure discredited for 20--30 years30 years
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24
Prospective studyProspective study
30 patients total (14 pain, 4 renal insufficiency, 30 patients total (14 pain, 4 renal insufficiency, 12 both)12 both)
Unilateral or bilateral cyst reduction sxUnilateral or bilateral cyst reduction sx
Followed for 21 months for pain and Cr Followed for 21 months for pain and Cr
Objective: Pain relief + Effect on Renal FunctionObjective: Pain relief + Effect on Renal Function
25
Pts with prePts with pre--operative renal dysfunction had operative renal dysfunction had
no change in declineno change in decline
Conclusions: PainConclusions: Pain
Effective pain relief in majority of ptEffective pain relief in majority of pt’’ss
80% at 1 year80% at 1 year
65% at 2 years65% at 2 years
In those who recurred, less intense than In those who recurred, less intense than
prepre--operativelyoperatively
26
Conclusions: Renal FunctionConclusions: Renal Function
No deleterious effect on renal functionNo deleterious effect on renal function
No improvement in renal functionNo improvement in renal function
Does not change progression of renal Does not change progression of renal
decline in predecline in pre--existing CRFexisting CRF
In unilateral cases no change from In unilateral cases no change from
contralateral kidneycontralateral kidney
27
15 patients15 patients
Unilateral 9Unilateral 9
Bilateral 6Bilateral 6
Followed BP, Cr, Analog Pain ScoresFollowed BP, Cr, Analog Pain Scores
Mean f/u 2.2 yearsMean f/u 2.2 years
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Results: PainResults: Pain
73% overall reported an improvement at 73% overall reported an improvement at
mean 2.2 yearsmean 2.2 years
In responders mean improvement 62%In responders mean improvement 62%
In failure ptIn failure pt’’s 2/15 had late failuress 2/15 had late failures
Bilateral had better result (83%) vs Bilateral had better result (83%) vs
unilateral (67%)unilateral (67%)
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Results: Cr and BPResults: Cr and BP
27% cured/improved HTN27% cured/improved HTN
33% worse HTN33% worse HTN
40% no change HTN40% no change HTN
No significant effect on CrNo significant effect on Cr
Results: ComplicationsResults: Complications
Urinoma in 3 Urinoma in 3 –– JJ stent for 4 weeksJJ stent for 4 weeks
Bilateral pleural effusion in 1 Bilateral pleural effusion in 1 –– treated treated
medicallymedically
Urine retention in 1 Urine retention in 1
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ConclusionsConclusions
Pain relief similar to large open series Pain relief similar to large open series (Barry and Elzinga 1992)(Barry and Elzinga 1992)
Better result with bilateral vs unilateralBetter result with bilateral vs unilateral
No worsening of renal functionNo worsening of renal function
No effect on BPNo effect on BP
Longer OR time than openLonger OR time than open
Decreased hospital stayDecreased hospital stay
Increased complicationsIncreased complications
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35 LCD procedures over 6 years (6 35 LCD procedures over 6 years (6
bilateral and 23 unilateral)bilateral and 23 unilateral)
Every cyst >2mm on / near surface txEvery cyst >2mm on / near surface tx
Followed pain analog scores, BP and CrFollowed pain analog scores, BP and Cr
Mean f/u 32 monthsMean f/u 32 months
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Results: PainResults: Pain
63%63%47%47%58%58%% %
reduction in reduction in
pain scorepain score
81%81%52%52%73%73%% pt% pt’’s with s with
pain relief pain relief
>50%>50%
36 months36 months24 months24 months12 months12 months
Results: Early ComplicationsResults: Early Complications
10 peri10 peri--operative complications (3 major 7 operative complications (3 major 7 minor)minor)
3 developed urinoma 3 developed urinoma –– stent for 4 weeksstent for 4 weeks
2 ileus2 ileus
1 atelectasis1 atelectasis
1 urine retention1 urine retention
1 pleural effusion treated medically1 pleural effusion treated medically
1 persistent pain1 persistent pain
1 spinal headache1 spinal headache
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Results: HTNResults: HTN
5/21 became normotensive5/21 became normotensive
9/21 had 49% reduction in ATI9/21 had 49% reduction in ATI
6/21 had worsening HTN6/21 had worsening HTN
Results: Renal functionResults: Renal function
No improvementNo improvement
In ptIn pt’’s with poor renal function or declining s with poor renal function or declining
function prefunction pre--operatively MIS decortication operatively MIS decortication
will not slow or stabilize itwill not slow or stabilize it
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Results: Late ComplicationsResults: Late Complications
1 pt developed abscess 6 months post1 pt developed abscess 6 months post--
operatively operatively –– nephrectomizednephrectomized
1 pt died of MI after bilateral 1 pt died of MI after bilateral
nephrectomies for recurrent / persistent nephrectomies for recurrent / persistent
painpain
4 pt4 pt’’s aged 15s aged 15--19 yrs19 yrs
Pain refractory to narcoticsPain refractory to narcotics
Mean f/u 11.5 monthsMean f/u 11.5 months
Bieri modified pain scaleBieri modified pain scale
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Results: Pain ScoresResults: Pain Scores
PrePre--Op pain scores 6Op pain scores 6--9 / 109 / 10
Score 0Score 0--1 / 10 at discharge1 / 10 at discharge
Score 0Score 0--1 / 10 at mean f/u 11.5 months1 / 10 at mean f/u 11.5 months
ComplicationsComplications
1 pt had renal pelvic urine leak requiring 1 pt had renal pelvic urine leak requiring
stenting for 6 weeksstenting for 6 weeks
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ConclusionsConclusions
FeasibleFeasible
Good short term Good short term
resultsresults
Longer f/u and larger Longer f/u and larger
series required for series required for
definitive conclusionsdefinitive conclusions
ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
39
ESRDESRD
On average occurs between 4On average occurs between 4thth--66thth decadedecade
Later in PKD2 than PKD1Later in PKD2 than PKD1
Once begins, average decline 5ml/min / Once begins, average decline 5ml/min /
year in CrClyear in CrCl
50% develop renal failure by age 6050% develop renal failure by age 60
ESRD: EtiologyESRD: Etiology
Not completely understoodNot completely understood
Only about 1% of nephrons develop cystsOnly about 1% of nephrons develop cysts
Pressure atrophy?Pressure atrophy?
HTN?HTN?
Increased apoptosis in nephronsIncreased apoptosis in nephrons
Vascular remodelingVascular remodeling
Analgesic nephropathyAnalgesic nephropathy
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ESRD: Risk FactorsESRD: Risk Factors
1.1. PKD1 typePKD1 type
2.2. MaleMale
3.3. African AmericanAfrican American
4.4. Hematuria <30 yearsHematuria <30 years
5.5. HTN <35 yearsHTN <35 years
6.6. HyperlipidemiaHyperlipidemia
7.7. Low HDLLow HDL
8.8. Sickle cell traitSickle cell trait
9.9. SmokingSmoking
10.10. Rate of cyst growth / size of kidneysRate of cyst growth / size of kidneys
11.11. Multiple pregnanciesMultiple pregnancies
ESRD: PreventionESRD: Prevention
ACEI slow rate of proteinuria but no effect ACEI slow rate of proteinuria but no effect
on Cr compared to CCB, HCZTon Cr compared to CCB, HCZT
Cyst unroofing has no effect Cyst unroofing has no effect
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ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
Infected CystsInfected Cysts
90% occur in women90% occur in women
Ascending infectionsAscending infections
E. coli, Klebsiella, Proteus and PseudomonasE. coli, Klebsiella, Proteus and Pseudomonas
Instrumentation a major risk factorInstrumentation a major risk factor
Poor antibiotic penetration Poor antibiotic penetration
R/O ObstructionR/O Obstruction
Lipophillic antibiotics (Flouroquinolones, Septra, Lipophillic antibiotics (Flouroquinolones, Septra, Chloramphenicol)Chloramphenicol)
Percutaenous cyst aspirationPercutaenous cyst aspiration
NephrectomyNephrectomy
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AUAUS Lesson 13 2001
ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
43
ADPKD: StonesADPKD: Stones
55--10 times the incidence of general 10 times the incidence of general
populationpopulation
30% of pt30% of pt’’s develop stoness develop stones
20% of pt20% of pt’’s are symptomatics are symptomatic
Contemporary endourological Contemporary endourological
managementmanagement
ADPKD: Renal ManifestationsADPKD: Renal Manifestations
HTNHTN
PainPain
ESRDESRD
Infected cystsInfected cysts
StonesStones
HematuriaHematuria
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Hematuria Hematuria
50% of ADPKD pt50% of ADPKD pt’’s s
Presenting symptom in 25%Presenting symptom in 25%
Hematuria a/w worsening CrHematuria a/w worsening Cr
Case reportCase report
Despite bed rest and 10 units blood transfusion Despite bed rest and 10 units blood transfusion
pt became unstablept became unstable
TXA 20mg/kg infused while awaiting ORTXA 20mg/kg infused while awaiting OR
Hematuria ceased Hematuria ceased
TXA continued for 2 monthsTXA continued for 2 months
No recurrence for 24 monthsNo recurrence for 24 months
45
Transexamic AcidTransexamic Acid
Plasminogen inhibitor Plasminogen inhibitor –– antifibrinolytic antifibrinolytic
agentagent
Reversibly blocks lysine binding sites on Reversibly blocks lysine binding sites on
plasmin moleculeplasmin molecule
Used during orthopedic and cardiac Used during orthopedic and cardiac
surgerysurgery
Used for bleeding duodenal and gastric Used for bleeding duodenal and gastric
ulcersulcers
Transexamic AcidTransexamic Acid
Urokinase activity often high in cysts Urokinase activity often high in cysts ––
fibrinolysisfibrinolysis
APPKD ptAPPKD pt’’s with CRF likely have local and s with CRF likely have local and
systemic hyperfibrinolysissystemic hyperfibrinolysis
Consider using in cases of severe Consider using in cases of severe
hematuria in ADPKDhematuria in ADPKD
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ADPKD: Transplant IssuesADPKD: Transplant Issues
1.1. When to consider transplantationWhen to consider transplantation
2.2. When to consider native nephrectomyWhen to consider native nephrectomy
3.3. Timing of native nephrectomyTiming of native nephrectomy
4.4. Issues unique to ADPKD after RTIssues unique to ADPKD after RT
When to consider transplantWhen to consider transplant
1.1. GFR < 10cc/minGFR < 10cc/min
2.2. Cr > 800umol/lCr > 800umol/l
3.3. Symptomatic uremiaSymptomatic uremia
47
Indications for Native Nephrectomy Indications for Native Nephrectomy
1.1. Chronic painChronic pain
2.2. HTNHTN
3.3. Cyst infectionsCyst infections
4.4. Renal massRenal mass
5.5. GI (Early satiety, constipation)GI (Early satiety, constipation)
6.6. No room for renal allograftNo room for renal allograft
7.7. Respiratory compromiseRespiratory compromise
8.8. Recurrent calculiRecurrent calculi
Native NephrectomyNative Nephrectomy
Rate of native nephrectomy for ADPKD Rate of native nephrectomy for ADPKD
decreased over last 3 decadesdecreased over last 3 decades
85% in 197085% in 1970’’ss
47% in 198047% in 1980’’ss
20% contemporary series20% contemporary series
Better conservative management Better conservative management
(improved abx, analgesics, MIS (improved abx, analgesics, MIS
techniques)techniques)
48
Native NephrectomyNative Nephrectomy
Current consensus is to avoid native Current consensus is to avoid native
nephrectomy if possiblenephrectomy if possible
Less complications on dialysisLess complications on dialysis
Improved survival on dialysisImproved survival on dialysis
EPO productionEPO production
Risk of blood transfusion Risk of blood transfusion –– sensitizationsensitization
Timing of Native NephrectomyTiming of Native Nephrectomy
49
Retrospective analysis Retrospective analysis
Matched ptMatched pt’’s with similar characteristicss with similar characteristics
Group 1: Concomitant RT and BL Nx (10)Group 1: Concomitant RT and BL Nx (10)
Group 2: RT only (9)Group 2: RT only (9)
Group 3: Staged BL Nx and RT (4 ptGroup 3: Staged BL Nx and RT (4 pt’’s, 3 s, 3
after and 1 before)after and 1 before)
PeriPeri--operative parameters and Croperative parameters and Cr
50
ConclusionsConclusions
Increased blood loss and transfusion in Increased blood loss and transfusion in
concomitantconcomitant
Lower complications in concomitantLower complications in concomitant
No difference in graft functionNo difference in graft function
No cases of DGF in concomitant groupNo cases of DGF in concomitant group
Increased pt satisfaction (non validated Increased pt satisfaction (non validated
questionnaire)questionnaire)
51
Retrospective review of 32 ptRetrospective review of 32 pt’’s over 12 yrss over 12 yrs
Group 1: PreGroup 1: Pre--transplant = 7 pttransplant = 7 pt’’ss
Group 2: Concomitant = 16 ptGroup 2: Concomitant = 16 pt’’ss
Group 3: PostGroup 3: Post--transplant = 9 pttransplant = 9 pt’’ss
Materials and MethodsMaterials and Methods
25 of 32 underwent bilateral nephrectomy25 of 32 underwent bilateral nephrectomy
Examined periExamined peri--operative course, OR time, operative course, OR time,
EBL, and effect on CrEBL, and effect on Cr
52
53
ResultsResults
No difference between 3 groups;No difference between 3 groups;
��ComplicationsComplications
��Blood lossBlood loss
��Hospital stayHospital stay
ConclusionsConclusions
Concomitant native nephrectomy is safe Concomitant native nephrectomy is safe
and does not compromise graft and does not compromise graft
Similar periSimilar peri--operative morbidity compared operative morbidity compared
to pre or postto pre or post
54
Timing of Native Nephrectomy: Timing of Native Nephrectomy:
SummarySummary
Best to avoid nephrectomy if possible Best to avoid nephrectomy if possible
(especially in pre(especially in pre--dialysis patients)dialysis patients)
Concomitant nephrectomy safeConcomitant nephrectomy safe
Concomitant nephrectomy avoids dialysis Concomitant nephrectomy avoids dialysis
in prein pre--dialysis living donor ptdialysis living donor pt’’ss
Concomitant nephrectomy in dialysis ptConcomitant nephrectomy in dialysis pt’’s s
avoids the increased morbidity of anephric avoids the increased morbidity of anephric
ptpt’’s on dialysiss on dialysis
Issues Unique to ADPKD Post RTIssues Unique to ADPKD Post RT
ADPKD have graft survival outcomes similar to ADPKD have graft survival outcomes similar to
RT population as a wholeRT population as a whole
The following were more prevalent;The following were more prevalent;
1.1. Diverticulitis +/Diverticulitis +/-- perforationperforation
2.2. Arachnoid hemorrhage (no CVAArachnoid hemorrhage (no CVA’’s overall)s overall)
3.3. Erythrocytosis with need for phlebotomyErythrocytosis with need for phlebotomy
No increased risk of cardiovascular diseaseNo increased risk of cardiovascular disease
55
Acquired Renal Acquired Renal
Cystic DiseaseCystic Disease
Acquired Renal Cystic DiseaseAcquired Renal Cystic Disease
1.1. DescriptionDescription
2.2. EpidemiologyEpidemiology
3.3. DiagnosisDiagnosis
4.4. HistopathologyHistopathology
5.5. SymptomsSymptoms
6.6. TransplantTransplant
7.7. Association with RCCAssociation with RCC
56
DescriptionDescription
Cysts forming in nonCysts forming in non--cystic failing or failed cystic failing or failed
kidneyskidneys
Originally thought to be HD onlyOriginally thought to be HD only
HD = PD > ESRD onlyHD = PD > ESRD only
Kidneys initially shrink after dialysis started Kidneys initially shrink after dialysis started
then increase after 3 years (Ishikawa then increase after 3 years (Ishikawa
1985)1985)
ARCD: EpidemiologyARCD: Epidemiology
8% at start of dialysis8% at start of dialysis
1010--20% 120% 1--3 years3 years
60% at 3 years of dialysis60% at 3 years of dialysis
90% between 590% between 5--10 years on dialysis10 years on dialysis
100% at 10 years dialysis100% at 10 years dialysis
ACRD 2.9:1 male to female ratioACRD 2.9:1 male to female ratio
57
ARCD: Risk FactorsARCD: Risk Factors
1.1. Length of time on dialysis or with ESRDLength of time on dialysis or with ESRD
2.2. Male > FemaleMale > Female
3.3. NephrosclerosisNephrosclerosis
4.4. African Americans > CaucasiansAfrican Americans > Caucasians
DiagnosisDiagnosis
U/S U/S
CT CT
MRIMRI
>3cysts per kidney>3cysts per kidney
Macroscopic cystic structures comprising Macroscopic cystic structures comprising
>25% of parenchyma>25% of parenchyma
Pope Urology 1994
58
HistolopathologyHistolopathology
Cysts size is mmCysts size is mm’’s to several cms to several cm’’ss
Pathogenesis unclearPathogenesis unclear
Blocked tubules (ischemia, sloughing, Blocked tubules (ischemia, sloughing,
crystals, fibrosis) ?crystals, fibrosis) ?
Uremic growth factors / cystogenic growth Uremic growth factors / cystogenic growth
factor not cleared by dialysis ?factor not cleared by dialysis ?
Symptoms / ComplicationsSymptoms / Complications
PainPain
HematuriaHematuria
InfectionsInfections
Malignancy riskMalignancy risk
59
ARCD and TransplantARCD and Transplant
Early transplant may prevent developmentEarly transplant may prevent development
Cysts may regress following transplantCysts may regress following transplant
Cysts may still develop after transplantCysts may still develop after transplant
Risk of RCC falls after transplantation (still Risk of RCC falls after transplantation (still
0.50.5--3.9% at a mean of 6 years)3.9% at a mean of 6 years)
Allografts become susceptible to ACKD Allografts become susceptible to ACKD
with chronic rejectionwith chronic rejectionIshikawa Am J Nephrology 1983
Vaziri Nephron 1984
Faber Lancet 1984
Ishikawa Nephron 1991
ESKD: Association with RCCESKD: Association with RCC
Population incidence of RCC 0.04%Population incidence of RCC 0.04%
11--3% prevalence of RCC in dialysis population3% prevalence of RCC in dialysis population
Incidence of RCC in ESRD 20 times population Incidence of RCC in ESRD 20 times population
risk in Japanrisk in Japan
Incidence of RCC 3Incidence of RCC 3--6 times population risk in 6 times population risk in
USAUSA
Annual incidence increases per time on dialysisAnnual incidence increases per time on dialysis
Ishikawa Nephron 1991
Matson Medicine 1990
60
ACKD: Association with RCCACKD: Association with RCC
2020--25% of ESRD with ARCD have 25% of ESRD with ARCD have
adenomasadenomas
When RCC develops in ESRD When RCC develops in ESRD –– a/w a/w
ARCD 80% of timeARCD 80% of time
Prevalence of RCC in setting of ESRD + Prevalence of RCC in setting of ESRD +
ARCD = 2ARCD = 2--7%7%
Mean time on dialysis is 8Mean time on dialysis is 8--9 years9 years
Biology of RCC in ESRDBiology of RCC in ESRD
Younger age of occurrence (5years)Younger age of occurrence (5years)
Male > Female by 7:1Male > Female by 7:1
Much higher incidence than general populationMuch higher incidence than general population
Smaller tumorsSmaller tumors
Less likely to have mets at diagnosis (15% vs Less likely to have mets at diagnosis (15% vs 2020--30%)30%)
Less aggressive course and better prognosisLess aggressive course and better prognosis
Papillary subtype more common (50% of cases)Papillary subtype more common (50% of cases)
More often multifocalMore often multifocal
61
Pathogenesis of RCC in ARCDPathogenesis of RCC in ARCD
Loss of nephronsLoss of nephrons
��
Hypertrophic changes + Hypertrophic changes + ‘‘unknown uremiaunknown uremia--related growth factorsrelated growth factors’’
��
Undifferentiated tubular growthUndifferentiated tubular growth
��
��risk of mutationrisk of mutation
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Proliferative activity of RCC in ESRD with Proliferative activity of RCC in ESRD with
ARCD vs Typical RCCARCD vs Typical RCC
SS--Phase, Ploidy, Proliferating Cell Nuclear Phase, Ploidy, Proliferating Cell Nuclear
Antigen (PCNA) Antigen (PCNA)
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ResultsResults
100% RCC100% RCC--ACDK had diploidACDK had diploid
56% RCC56% RCC--T had diploid T had diploid –– 44% aneuploid44% aneuploid
RCCRCC--A group A group –– same fraction in each same fraction in each
mode of cell cycle as normal renal tissuemode of cell cycle as normal renal tissue
PCNA higher in RCCPCNA higher in RCC--Typical than RCCTypical than RCC--AA
ConclusionsConclusions
Histological characteristics correlate with Histological characteristics correlate with
observation that RCC in ARCD less observation that RCC in ARCD less
aggressive than typical RCCaggressive than typical RCC
Potential flaw Potential flaw –– compared smaller RCCcompared smaller RCC’’s s
in ARCD to larger typical RCCin ARCD to larger typical RCC’’ss
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ARCD : ScreeningARCD : Screening
Controversy exists about screening the dialysis Controversy exists about screening the dialysis population for RCCpopulation for RCC
Does cost of screening outweight the potential Does cost of screening outweight the potential benefits?benefits?
Risk of dying from coRisk of dying from co--morbid conditions?morbid conditions?
What screening modality should be used?What screening modality should be used?
When to start screening?When to start screening?
What is the life expectancy of dialysis patients in What is the life expectancy of dialysis patients in that region?that region?
Are patients candidates for therapy?Are patients candidates for therapy?
Continue screening after transplant?Continue screening after transplant?
ScreeningScreening
Proponents start screening after 3 years Proponents start screening after 3 years
dialysis dialysis –– marked increase in ARCD after marked increase in ARCD after
this pointthis point
Then every other year with U/SThen every other year with U/S
CECT if suspicious findingsCECT if suspicious findings
The longer the pt is on dialysis the higher The longer the pt is on dialysis the higher
the PPV of screeningthe PPV of screening
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Screening: SummaryScreening: Summary
U/S most cost effectiveU/S most cost effective
U/S least morbid modalityU/S least morbid modality
Population to be screened and timeline not Population to be screened and timeline not
well definedwell defined
THE ENDTHE END
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