Inherited Disorders of the Kidney Flashcards
Most commonly, polycystic disease is autosomal ________
Most commonly, polycystsic disease is autosomal dominant
Which gene is most commonly affected to cause autosomal dominant polycystic kidney disease?
PKD1 (on chromosome 16) - 85% (most severe)
(PKD2 is second most common found on chromosome 4)
What does polycystic kidney disease involve?
Massive cyst enlargement creating large kidneys
Small populations of renal tubules give rise to epithelial lined cysts
Which type of tumour is commonly associated with polycystic kidney disease?
Benign adenomas (25%)
In patients with ADPKD, what is a very common early clinical feature?
Hypertension
Why does hypertension occur with ADPKD?
Blood vessels of nephrons become compressed causing reduced perfusion
The RAAS ois activated to raise blood pressure
What clinical features are associated with ADPKD?
Reduced ability to concentrate urine
Renal failure
Chronic pain
Hypertension
Haematuria (due to cyst rupture, cystitis, stones)
Cyst Infection
Which organ may also decline in functionality along with the kidneys during ADPKD?
Liver
(liver cysts can develop after renal cysts (around 10yrs))
How can the brain be affected in ADPKD?
Intracranial aneurysms
Besides the liver and brain, which other areas of the body exhibit extra-renal manifestations of ADPKD?
Valvular disease (mitral/aortic polapse, collagenous/myxomatous degeneration)
Diverticular disease
Abdominal/inguinal hernias
In which ways can ADPKD be diagnosed?
USS (bilateral cysts and renal enlargement)
CT/MRI (when unclear on USS)
Genetic testing
Generally, ADPKD will appear after what age?
20s
How is ADPKD differentiated from ARPKD in children/early cystic development?
USS showing congenital hepatic fibrosis suggests recessive disease
How is ADPKD managed?
Control risk factors
- Hypertension must be controlled strictly
- Hydration
- Proteinuria reduction
- Cyst haemorrhage and infection management
Tolvaptan - reduces cyst volume and progression
When renal failure occurs with ADPKD, what are the management options?
Dialysis
Transplantation
Must be aware to manage cardiovascular and cerebrovascular causes of death
ARPKD tends to present ________
ARPKD tends to present early
What does ARPKD generally present with as well as renal cysts?
Hepatic lesions
Which gene is the cause of ARPKD?
PKDH1 (Chromosome 6)
ARPKD is generally _________ and ___________
ARPKD is generally symmetrical and bilateral
Where do the cysts in ARPKD histologically develop from?
Collecting duct system
In ARPKD the kidneys are _________ palpable
In ARPKD the kidneys are always palpable
Overall which type of PKD is more severe?
ADPKD
Which two clinical features are classical of ARPKD?
Recurrent UTIs
Hypertension
Alport syndrome involves a mutation in which gene?
COL4A3, COL4A4, COL4A5 gene
What causes the renal problems in Alport syndrome?
Disorder of type IV collagen matrix
In most cases, how is Alport syndrome inherited?
X-linked
(COL4A5 mutation)
Which clinical features would causes suspicion of Alport syndrome?
Haematuria (gross or unexplained microscopic)
Sensorineural deafness
Ocular defects (anterior lenticonus)
Leiomyomatosis of oesophagus/genitalia (rare)
Why does haematuria occur with Alport syndrome?
Type IV collagen is missing or dysfunctional
This causes the GBM to become thin and very porous
Red blood cells then pass through causing (normally) microscopic haematuria
What is the classical presentation of Alport syndrome on biospy?
Thickening of the GBM with splitting of the lamina densa (electron microscopy)
Why does proteinuria occur in Alport syndrome and what does it eventually lead to?
Thin and porous GMB eventually lets proteins through
Proteinuria increases and along with other factors causes the GBM to undergo sclerosis
Which type of hearing loss is associated with Alport syndrome?
Conductive
(abnormal type IV collagen may prevent hair cells generating normal nerve signals)
What is anterior lenticonus?
Central part of the lens bulges into the anterior chamber as it lacks integrity to maintain lens shape
What is the management for Alport syndrome?
BP management
Transplant/dialysis
Which condition is defined as an inborn error of glycosphingolipid metabolism and what is its cause?
Anderson Fabrys disease
(deficiency of a-galactosidase A)
Which organs are affected in Anderson Fabrys disease?
- Kidneys
- Liver
- Lungs
- Red blood cells
How is Anderson Fabrys disease inherited?
X-linked
In which ways can Anderson Fabrys disease be diagnosed?
- Plasma/Leukocyte a-GAL activity
- Renal Biopsy
- Skin Biopsy
What are the clinical features associated with Anderson Fabrys disease?
- Renal failure
- Cutaneous (Angiokeratomas often seen in umbilical region)
- Cardiac (cardiomyopathy, valvular disease)
- Neurological (stroke, acroparaesthesia)
- Psychiatric
What is the classical appearance of angiokeratomas?
Clusters of dark-red to blue angiokeratomas (telangiectasia) in the umbilical area
How can Anderson Fabry disease be treated?
- Enzyme replacement (Fabryzyme)
- Management of complications
How is medullary cystic kidney inherited?
AD
Medullary cystic kidney disease has what pathogenesis?
Genetic mutation (AD) causes abnormal renal tubules
Fibrosis and cysts occur as a result
Where do cysts occur in medullary cystic kidney disease?
Corticomedullary junction/medulla
How can medullary cystic kidney disease be diagnosed?
CT
How is medullary cystic kidney disease treated?
Transplant
What are the hallmark features of medullary sponge kidney?
Development of multiple fluid filled cysts in the medulla of the kidney
(gives sponge appearence)
Dilated collecting ducts
What are the complications of medullary sponge kidney?
Kidney stones
Metabolic acidosis
UTI (stagnant urine)
How is medullary sponge kidney diagnosed?
Excretion urography
How is medullary sponge kidney treated?
Hydration + citrate supplements (prevent stone formation)
Bicarbonate (prevents calcium leaching out of bones)
Antibiotics (in the event of UTIs)
