Cystic Kidney Disease Flashcards
Name the types of cystic kidney disease
Hereditary Hereditary polycystic kidney diseases • ADPKD • ARPKD Cystic diseases of the renal medulla • Medullary cystic disease and nephronophthisis • Medullary sponge kidney Miscellaneous hereditary renal cystic disorders • Tuberous sclerosis • Von Hippel-Lindau Disease
Developmental
• Agenesis (failure to develop) of one kidney
• Hypoplastic (incomplete development) kidneys
• Renal dysplasia: disordered anatomic and histologic structure
Acquired
• CKD
• Dialysis
• Aging (Cysts usually in proximal tubules, benign, < 3 cm size)
Explain the pathogenesis of cyst formation
o Normal growth: balance between cell proliferation and apoptosis
o Polycystic kidneys: dysregulated processes → cysts form with undifferentiated or immature epithelia
o Increased burden of apoptosis → destroys functional parenchyma, allows cystic epithelia to proliferate
o BM next to cyst thickens
o Inflammatory cells in interstitium
o Cyst may separate or stay attached
o Transepithelial fluid secretion → fluid accumulates in cyst
o In hereditary disease:
• Na+/K+ ATPase pump abnormally on apical membrane (instead of basolateral) → fluid secretion
Autosomal Dominant PKD: Inheritance
Autosomal dominant
-Most common type of hereditary kidney disease worldwide
- PKD-1 (85% cases) = on chromosome 16; codes for Polycystin-1 (membrane receptor in adherens junctions and focal adhesions); more severe form
- PKD-2 (15%) = on chromosome 4; Polycystin-2 (transmembrane Ca2+ ion channel); less severe form
Autosomal Dominant PKD: Age of onset
30-50
Autosomal Dominant PKD: Clinical Signs
-Variable presentation
Renal symptoms:
- Cysts anywhere in nephron
- Bilaterally and uniformly cystic and enlarged kidneys
- Hematuria (microscopic or gross)
- Decreased urine concentration → Nocturia
- HT (RAAS activation due to stretched arterioles)
- Flank pain (acute or chronic) from stones (20-30%; uric acid & oxalate) or cysts increasing in size or rupture
- UTI/ pyelonephritis
- Polycythemia (from increased EPO production)
- Anemia
Non-renal symptoms:
- GI: colonic diverticula, abdominal wall hernia
- Liver cysts (50%), usually benign; normal liver function tests
- Subarachnoid hemorrhage: berry aneurysm
- Mitral valve disease
- Drooping upper eyelids
- Seminal vesicle, pancreatic, splenic cysts
Autosomal Dominant PKD: Mean age of progression
PKD1: 53 yrs
PKD2: 69 yrs
Factors affecting progression rate:
- Gene involved
- Male gender
- HT
- UTI’s
- Drugs (NSAIDs
Autosomal Dominant PKD: diagnosis
- Family history
- UA, serum creatinine, anemia, polycythemia
- Imaging: US, CT, MRI:
• 60: 4 cysts/ kidney
-Genetic testing: living-related kidney donors, equivocal imaging, desire to know
-If no cyst at age 30 = no risk of disease
Autosomal Dominant PKD: treatment
-No curative treatment
Pre-ESRD:
- BP and proteinuria control
- ACEI/ARB to prevent hyper-filtration/ fibrosis
- Avoid contact sports
ESRD:
- Transplantation
- Dialysis
- Nephrectomy
Autosomal Recessive PKD: Inheritance
Autosomal recessive, with variable expression
- PKDH-1 on chromosome 6; codes for Fibrocystin (transmembrane protein)
- Mutation → abnormal C-terminal, affects intracellular signaling
Autosomal Recessive PKD: Age of onset
-Childhood (1st year of life)
Autosomal Recessive PKD: Clinical Signs
- Fusiform dilation of collecting ducts
- Liver cysts, fibrosis, dilation, hyperplasia of bile ducts → portal HT
- Periportal fibrosis, lung abnormalities (pulmonary hypoplasia)
Autosomal Recessive PKD: Mean age of progression
-High mortality (9-24% die within 1st yr)
Autosomal Recessive PKD: Diagnosis
-US (antenatal in severe cases)
Autosomal Recessive PKD: Treatment
- Supportive
- Control HT (ACEI, CCB, BB, diuretics)
- Dialysis
- Transplantation
Nephronophthisis (NPHP): Inheritance
Autosomal Recessive
- 8 genes: NPHP 1-8
- Codes for protein Nephrocystin
Nephronophthisis (NPHP): age of onset
Childhood
Nephronophthisis (NPHP): Clinical signs
- Impaired urinary concentrating ability
- Disruptions of tubular BM
- Tubulointerstitial fibrosis and renal cysts
- Salt and water wasting
- Medullary cysts
- HT
- Growth retardation
- Small kidneys
- Anemia
Extra renal:
- Hepatic fibrosis
- Retinal Disease
- Bone Disease
Nephronophthisis (NPHP): mean age of progression
Before age 20
Nephronophthisis (NPHP): treatment
- Dialysis
- Transplantation
Medullary Cystic Kidney Disease (MCKD): inheritance
Autosomal dominant (Rare) -Chromosomal 1q21 and 16p12
Medullary Cystic Kidney Disease (MCKD): age of onset
Early adulthood
Medullary Cystic Kidney Disease (MCKD): clinical signs
- Impaired urinary concentrating ability
- Disruptions of tubular BM
- Tubulointerstitial fibrosis and renal cysts
- Salt and water wasting
- Polyuria, polydipsia
- Hyperuricemia and gout
- Small kidneys
- Medullary cysts
Medullary Cystic Kidney Disease (MCKD): mean age of progression
Age 20-60
Medullary Cystic Kidney Disease (MCKD): diagnosis
- Family history
- Clinical suspicion
- US
- Renal biopsy
- Genetic testing
Medullary Cystic Kidney Disease (MCKD): treatment
- Dialysis
- Transplantation
Medullary Sponge Kidney: inheritance
Hereditary (some autosomal dominant inheritance pattern) or Developmental
-Common disease
-More frequent in women
Medullary Sponge Kidney: age of onset
-Average age of diagnosis = 27 years
Medullary Sponge Kidney: clinical signs
- Cystic dilation of terminal Collecting Duct (pericalyceal region, renal pyramids) = brush-like appearance
- Typically diffuse and bilateral cysts
- Most patients asymptomatic
- Common complications: kidney stones, hematuria, UTI
Medullary Sponge Kidney: mean age of progression
- Benign course (NO progression to renal failure)
Medullary Sponge Kidney: diagnosis
- Accidental
- Renal stones
- Hematuria (microscopic)
- UTIs
- Decreased concentrating ability
Medullary Sponge Kidney: treatment
-Symptomatic, based on complications
Tuberous Sclerosis or TS Complex (TSC): inheritance
- Autosomal dominant neurocutaneous disease
- *Majority of cases due to new mutations
- Mutation in hamartin or tuberin proteins
Tuberous Sclerosis or TS Complex (TSC): age of onset
-Typically diagnose <7 years
Tuberous Sclerosis or TS Complex (TSC): clinical signs
- Hamartomeas and angiomyolipomas (tubers) deposited in body (skin, brain, kidneys, etc)
- Benign tumors
- Brain symptoms: seizures, mental retardation, adenoma sebaceum
Renal manifestations:
- Angiomyolipomas: bilaterally, large amounts; when >4 cm → pain, bleeding into a lesion, hematuria
- Benign cysts (20-30%)
- HT (renin-dependent)
- CKD
- Renal cell carcinoma
Tuberous Sclerosis or TS Complex (TSC): mean age of progression
Progressive disease:
-25% die <25 years
-Common causes of death: CNS tumors and kidney failure
Tuberous Sclerosis or TS Complex (TSC): diagnosis
-Imaging: CT, US
Tuberous Sclerosis or TS Complex (TSC): treatment
- BP and renal function monitoring
- Renal US or CT to monitor
- Symptomatic treatment
- Surgical resection of concerning tumors
Von Hippel-Lindau Syndrome: inheritance
- Autosomal dominant
- Very rare
- Gene on short arm of chromosome 3
- Follows 2-hit model
Von Hippel-Lindau Syndrome: clinical signs
- Multiple visceral cysts: pheochromocytomas, liver, kidney, and pancreas cysts
- Cysts = pre-malignant (40% develop clear-cell renal carcinoma)
- hemangioblastomas of CNS and retina
Von Hippel-Lindau Syndrome: mean age of progression
-High mortality (49 years)
Von Hippel-Lindau Syndrome: diagnosis
- CT, MRI, US = detect primary tumors
- Genetic testing
Von Hippel-Lindau Syndrome: treatment
- Regular renal surveillance
- Renal-sparing removal of renal mass (surgical treatment)
