CYSTIC DISEASE

Pediatric GU Review

UCSD Pediatric UrologyGeorge Chiang MD

Sara Marietti MD

Outlined from The Kelalis-King-Belman Textbook of Clinical Pediatric Urology 2007

(not for reproduction, distribution, or sale without consent)

Definitions

• Abnormal sac or dilated duct within the kidney lined by epithelium

• Micro or macroscopic

• May communicate or be in continuity with the nephron, collecting duct or calyx

• +/- dysplasia

Categories

• Genetic– ARPKD– ADPKD– Juvenile nephronophthisis-medullary cystic dz– Congenital nephrosis– Familial hypoplastic glomerulocystic kidney dz– VHL– Tuberous sclerosis

Categories

• Non-genetic–MCDK–Cystic Nephroma (benign multilocular cyst)–Simple cysts–Medullary sponge kidney–Sporadic glomerulocystic kidney dz–Acquired renal cystic dz–Calyceal diverticulum

Polycystic Kidney Disease

• Autosomal recessive polycystic kidney disease–Can appear in adolescents

• Autosomal dominant polycystic kidney disease–Can appear in infants

ARPKD

• Incidence – 1 in 5,000 to 40,000

• 2.1% of all childhood ESRD

• Mutation of PKHD1 on chromosome 6

• Cysts primarily in collecting ducts

• Associated liver findings–Congenital Hepatic Fibrosis

• Biliary ectasia• Periportal fibrosis• Portal hypertension

ARPKD

• In general–The more severe the ARPKD the milder the

CHF and vice versa

–The later the ARPKD presents the slower the progression to renal failure

–All pts will develop either renal failure or CHF or both

ARPKD - Kidneys

Large, Hyperechogenic

Large, Cystic

Smaller on Dialysis

ADPKD

• Incidence – 1 in 500 to 1,000

• Most prevalent hereditary renal disorder

• Accounts for 10-20% of pts on HD

• PKD1 – Chromosome 16

• PKD2 – Chromosome 4

• Cysts in any part of the kidney

ADPKD – Genetic Phenomenon

• Gene Imprinting–More severe when passed on by the

mother

• Gene Anticipation–Passed on progressively earlier and with

greater severity in subsequent generations

ADPKD - Kidneys

Large, Hyperechogenic or Cystic

Large, Cystic

Large, cystic on Dialysis

ADPKD – Severity/Mortality

• 40% of adults have no family history• 38% diagnosed have a parent who is unaware

they have the disease• 50% are diagnosed at autopsy• Incidence of renal failure

– By age 40 – 2%, age 50 – 23%, age 73 – 48%

• Mortality– Infants – renal failure– Adults – renal failure, HTN, Cerebral hemorrhage

ADPKD – Renal Complications

• Hypertension - >80% with ESRD

• Hematuria – 50%

• Pain – 15-60%

• UTI – frequent

• Stones – 20%

• Nephromegaly – 100%

• Renal failure – 40% by age 60

ADPKD – Extra-Renal

• GI–Hepatic cysts -50%, increases with age–Pancreatic cysts–Colonic diverticuli

• Cardiovascular–Mitral valve prolapse– Intracranial aneurysms

Juvenile Nephronophthisis/Medullary

Cystic Disease Complex• Cysts at corticomedullary junction• JN – autosomal recessive

– Gene – NPH1,2,3 on chromosome 2– Leading cause of renal failure in teenagers

• MCD – autosomal dominant– Unknown genetic locus– Presents after age 20

• Both assoc with interstitial nephritis

Tuberous Sclerosis

• Triad of adenoma sebaceum(75%), epilepsy (80%), and mental retardation(60%)

• Renal masses– Cysts – 20% (frequently before 3 yo)– RCC – 2%– AML – 50% (rare before 6yo)

• Autosomal dominant– TSC1 on chromosome 9– TSC2 on chromosome 16 – contiguous gene

syndrome

VHL

• Associated with cerebellar and retinal hemangioblastomas, cysts of pancreas, kidney(76%), and epididymis, pheo(10-12%), and RCC (50%)

• Autosomal recessive

• Chromosome 3 – tumor suppressor gene to regulate HIF

Multicystic Dysplastic Kidney

• Involves the entire kidney

• Always show primitive ducts on path – tubules encased by fibromuscular cells – nephron precursor

• 3 forms– Large cysts – bunch of grapes– Solid cystic dysplasia – small cysts– Hydronephrotic – prominent central medial cyst

MCDK

• Non-Renaform shape on imaging• Small cysts between the larger ones• Communication may not be visible but is

present• Associations

– Contralateral UPJ Obstruction – 3-12%– Contralateral VUR – 18-43%– HTN– Malignancy – Wilms’ tumor rare

MCKD

• National MCKD Registry U/S Follow Up

4-6 mos >5yrs

Not Identifiable 7.2% 23.9%

Smaller 65.7% 23.9%

Larger 5% 1.3%

Unchanged 22.1% 37.1%

Benign Multilocular Cyst (Cystic Nephroma)

• Well encapsulated• Unilateral and solitary• Multilocular• No communication between loculations• Non-dysplastic• Indistinguishable from Wilms’ tumor

variants by imaging• Diagnosis – by surgical excision

Benign Multilocular Cysts

• Before 4yo – 67% male

• After 30yo – 75% female

• Cysts lined by cuboidal/columnar epithelium and contain clear/straw colored fluid

• Septa composed of either fibrous tissue or immature (embryonic-type) tissue

Simple Cysts

• Incidence–0-18 yrs – 0.22%–40 yrs – 20%–60 yrs – 33%–50 yrs + (on autopsy) - >50%

Bozniak Classification

• Category I – good through transmission, no internal echoes, sharp smooth wall– No surgery

• Category II – some septation, minimal calcificaitons– No surgery

• Category IIF – significant calcification in the wall– No surgery

Bozniak Classification

• Category III – Prominent septation, thicker wall–Surgery

• Category IV – Irregular margins, solid enhancing elements, probably malignant–Surgery

Medullary Sponge Kidney

• Usually after age 20

• Hypercalciuria – 33-50%

• Renal colic – 50-60%

• UTI – 20-30% (more in females)

• Cystic lesions within collecting ducts

• Mild concentrating defect

Acquired Renal Cystic Disease

• Typically seen in renal failure patients but don’t have to be on HD

• Multiple bilateral small cysts–Usually less then 0.5cm but may be 2.5-

3cm–Some cysts associated with hyperplastic

epithelium–Calcium oxalate crystals in cyst wall

ARCD

• Pathogenesis– Obstruction of nephrons by

• Focal proliferation of tubular epithelium• Interstitial fibrosis• Intratubular oxalate crystals

– Accumulation of cystogenic substances

• Clinical Manifestations– Hemorrhage and hematuria– Infection and fever– Flank pain– Neoplasia

ARCD

• 10% of renal failure pts have renal adenomas

• 25% of ARCD pts have adenomas

• Risk of RCC in ESRD is 3-6x general population

• Risk of RCC in ESRD + ARCD >10x general population

QUESTIONS

The renal cystic condition that arises prior to the formation of the nephron is::

a) Autosomal recessive PCKD

b) Autosomal dominant PCKD

c) Medullary sponge

d) Multicystic kidney disease

e) Juvenile nephronophthisis

A 6 week old boy has a large palpable right abdominal mass. Ultrasound demonstrates a fluid-filled mass with multiple cystic lucencies. A renal scan shows no uptake of the right kidney and a normal left kidney. He has moderate respiratory distress and an elevated right hemidiaphragm. The most appropriate therapy is:

a) Right nephrectomy

b) Percutaneous aspiration of the cysts

c) Cystoscopy and RGP

d) Right pyeloplasty

e) observation

A 3 year old boy has a palpable abdominal mass. Ultrasound and CT scan demonstrates a multilocular cyst. The next step is:

a) Repeat u/s in one year

b) Cyst aspiration

c) Genetic testing

d) Tumor resection

e) MRI scan

Ultrasound of a newborn baby with an abdominal mass shows an enlarged kidney containing large cystic spaces that do not appear to communicate with one another. The best test to confirm the diagnosis is:

a) CT Scan

b) IVP

c) Retrograde pyelogram

d) DMSA renal scan

e) Antegrade pyelogram

Medullary sponge kidney is:

a) Cystic dilation of the distal convoluted tubules

b) A bilateral and hereditary renal abnormality

c) Characterized by hypocitraturia

d) Best diagnosed by IVP

e) A precursor of end stage renal disease

A 5 year old boy with hepatosplenomegaly develops progressive azotemia and a renal concentrating defect. Ultrasound of the kidneys demonstrates slight enlargement with multiple small (1-2 cm) cortical cysts. An uncle died of renal disease. The most likely diagnosis is:

a) Familial juvenile nephronopthisis

b) ARPKD

c) ADPKD

d) Tuberous sclerosis

e) Retinal-retinal dysplasia