Inherited Renal Disorders Flashcards
What are the two forms of polycystic disease?
Autosomal recessive or dominant (common)
What is the aetiology of autosomal dominant polycystic kidney disease?
Most frequent life threatening hereditary disease
Important cause of ESRD = 8-10% of ESRD in Europe and Australia
What are the mutations implicated in autosomal dominant PKD?
PKD1 (85%) and PKD2 (15%)
What are some features of the PKD1 mutation in autosomal dominant PKD?
Located on chromosome 16, patients develop end stage kidney failure at an earlier stage than PKD2 patients
Where is the PKD2 mutation of autosomal dominant PKD located?
Located on chromosome 14
What is the histological appearance of autosomal dominant PKD?
Massive cyst enlargement = large kidneys
Epithelial lined cysts arise from a small population of renal tubules
Benign adenomas occur in 25%
What are the renal features of autosomal dominant PKD?
Reduced urine concentrating ability
Chronic pain and renal failure
Haematuria = cyst rupture, cystitis, stones
Cyst infection
Hypertension = common, mean age of onset is 31
What is the most common extra-renal manifestation of autosomal dominant PKD?
Hepatic cysts = present 10 years after renal cysts, liver function generally preserved
What may hepatic cysts associated with autosomal dominant PKD cause?
SOB, pain and ankle oedema
What are some extra-renal manifestations of autosomal dominant PKD?
Hepatic cysts, intra-cranial aneurysms, cardiac disease, diverticular disease, hernias
What are some features of the intra-cranial aneurysms associated with autosomal dominant PKD?
4-8% of patients, seen in clusters in families, mainly in the anterior circulation territory, screening indicated if positive family history
What cardiac diseases are associated with autosomal dominant PKD?
Mitral or aortic valve prolapse
Valvular disease = collagenous/myxomatous degeneration
What are the features of diverticular disease associated with autosomal dominant PKD?
Increased prevalence and incidence of complications, usually patients on dialysis, may have diverticulitis or colonic perforation
How common are hernias in patients with autosomal dominant PKD?
45% of patients have inguinal hernias
Also increased incidence of abdominal hernias
What is the radiological diagnosis of autosomal dominant PKD?
US sounds shows prevalence of multiple bilateral cysts and renal enlargement, CT/MRI used if US unclear
How is genetic diagnosis used in autosomal dominant PKD?
Linkage analysis and mutation analysis
How does autosomal dominant PKD present in children?
Early onset = can be in utero or first year of life
Siblings are at increased risk of early disease
How are children affected by autosomal dominant PKD?
Renal involvement similar to adults but cerebral aneurysms are rare
Single cyst in high risk patient is enough for diagnosis
How can autosomal dominant PKD in children be differentiated from autosomal recessive PCK?
Using US = presence of congenital hepatic fibrosis is suggestive of recessive disease
What is the chance of the children of someone with autosomal dominant PKD developing the disease?
50%
When should genetic counselling be offered to patient with autosomal dominant PKD?
Both pre and post-testing is required in any patient at risk and who are planning to undergo diagnostic testing
What is the management of autosomal dominant PKD?
Rigorous hypertension control, hydration, proteinuria reduction, cyst haemorrhage or infection control, dialysis or transplant if renal failure
What new drug can be used to treat autosomal dominant PKD?
Tolvaptan = reduces cyst volume and progression
Who is primarily affected by autosomal recessive PKD?
Young children = commonly associated with hepatic lesions
What mutation causes autosomal recessive PKD?
Mutation in PKDH1 on chromosome 6
How are the kidneys involved in autosomal recessive PKD?
Bilateral and symmetrical renal involvement
Urinary tract usually normal
What is the histological appearance of autosomal recessive PKD?
Cysts are seen appearing from the collecting duct system = 30-90% of ducts involved depending on severity
What does the presentation of autosomal recessive PKD depend on?
Depends on renal/liver lesions
Must distinguish between severe forms and ones which survive the neonatal period
How does autosomal recessive PKD present?
Kidneys always palpable, hypertension, recurrent UTIs, slow decline in GFR (<1/3 reach dialysis)
What is the prognosis of autosomal recessive PKD?
30-50% are severely affected
Infants who survive neonatal period have mortality rate of 9-24% in the first year of life
Does the prognosis of autosomal recessive PKD improve after the first year of life?
Yes = survival of 80% beyond 15 years
What is Alports syndrome also known as?
Hereditary nephritis
How common is Alports syndrome?
1-2% of patients with end stage renal disease
What is Alports syndrome?
Disorder of type 4 collagen matrix = mutation in COL4A5 gene leads to deficient collagenous matrix
What is the inheritance of Alports syndrome?
X-linked inheritance in 85%
What is the characteristic feature of Alports syndrome?
Haematuria
What does proteinuria in Alports syndrome mean for prognosis?
Confers poor prognosis
What are the extra-renal manifestations of Alports syndrome?
Sensorineural deafness, ocular defects (anterior lenticonus), leiomyomatosis of oesophagus/genitalia (rare)
How does Alports syndrome appear on biopsy?
Variable thickness of GBM = characteristic feature
When should you suspect Alports syndrome?
In a patient with haematuria and hearing loss
How is Alports syndrome treated?
Non-specific = standard aggressive treatment of BP and proteinuria, dialysis or transplantation
What causes Anderson-Fabrys disease?
Inborn error of glycosphingolipid metabolism = deficiency of a-galactosidase A
What is Anderson-Fabrys disease?
X-linked lysosomal storage disease = rare
What is affected by Anderson-Fabrys disease?
Kidneys, liver, lungs, erythrocytes
What are the features of Anderson-Fabrys disease?
Renal failure, angiokeratomas, cardiomyopathy, valvular disease, stroke, acroparaesthesia, psychiatric
How is Anderson-Fabrys disease diagnosed?
Plasma/leukocyte a-GAL activity
Renal and skin biopsy = concentric lamellar inclusions with lymphocytes
How is Anderson-Fabrys disease treated?
Fabryzyme enzyme replacement
Management of complications
What is a medullary cystic kidney?
Rare inherited cystic disease = autosomal dominant
What are the features of a medullary cystic kidney?
Morphologically abnormal renal tubules leading to fibrosis, normal/small kidneys, cortex and medulla both shrunken
Where are cysts present in a medullary cystic kidney?
In the corticomedullary junction or medulla = not essential for diagnosis
How is a medullary cystic kidney diagnosed?
Family history and CT scan
What age do medullary cystic kidneys present at?
Presents on average at age 28
How is a medullary cystic kidney treated?
Renal transplant is treatment of choice
What are some features of a medullary sponge kidney?
Uncommon with sporadic inheritance
Renal failure unusual
What renal changes occur in a medullary sponge kidney?
Dilation of collecting ducts
Cysts have calculi
Medullary area appears like sponge in severe cases
How is a medullary sponge kidney diagnosed?
Excretion urography = to demarcate calculi
