Renal Cystic Disease; ADPKD Vs ARPKD Flashcards
What is renal cystic disease?
Solitary or multiple renal cysts are common, especially with advancing age; 50% of those over 50 have one or more such cysts
What are the different types of kidney cysts?
- Simple cysts - most common form - benign
- Polycystic - when there are a lot of them - can be bad
- Hydronephrosis - when ureter blocked and kidney dilates and gets bigger
- Dysplasia – when not formed properly
- Medullary sponge – dilation of collecting ducts
- Acquired cystic disease – medullary uraemic, dialysis cystic
What are the 2 forms of polycystic kidney disease?
- Autosomal dominant (ADPKD) - develops in adulthood
- Autosomal recessive (ARPKD) - rarer but worse - develops in childhood
What is ADPKD?
An autosomal dominant condition characterised by progressive cyst development.
Multiple cysts develop, gradually and progressively -> cysts increase in size -> renal enlargement + loss of function -> kidney tissue destruction -> kidney failure
A mutation in which genes can cause ADPKD?
- PKD1 gene on chromosome 16 (85%)
- PKD2 gene on chromosome 4 (15%)
What protein is mutated in polycystic disease?
What is its normal function?
What happens when it’s mutated?
Polycystin protein.
Normal:
Allows calcium influx to inhibit cell proliferation
Mutation:
Cell overproliferation + overexpression of H2O channels = fluid-formed cysts
Briefly explain the pathophysiology of ADPKD.
- PKD1 encodes polycystin 1 -> involved in cell-cell and/or cell-matrix
interactions - regulates tubular and vascular development in kidneys. - PKD2 encodes polycystin 2 which functions as a calcium ion channel.
- The polycystin complex occurs in cilia that are responsible for sensing flow
in the tubule. - Disruption of the polycystin pathway results in reduced cytoplasmic Ca2+
- In principal cells of the collecting duct, this causes defective ciliary
signalling and disorientated cell division -> resulting in cyst formation.
At what age do people with ADPKD normally present?
Normally present around 50 y/o.
Cysts increase in size with advancing age.
Give 4 signs of ADPKD.
- Hypertension.
- Haematuria.
- Polyuria.
- Abdominal/loin/ lower back pain.
- Palpable bilateral costo-vertebral masses.
- Kidney stones.
- Upper UTIs.
- Eventually, loss of kidney function (CKD).
What are 3 pathophysiological effects of the cysts in polycystic kidney disease?
- Compress blood flow – hypoperfusion – RAAS activation – hypertension
- Block the collecting ducts – stasis of urine – kidney stones
- Renal failure
Why might someone with ADPKD have bilateral palpable costo-vertebral masses?
Cysts increase in size and cause renal enlargement.
Often, the kidney’s can be HUGE!
Give 2 extra-renal manifestations of ADPKD.
- Polycystic liver disease.
- Intracranial aneurysms e.g. SAH
(Subarachnoid haemorrhage associated with berry aneurysm rupture)
How can ADPKD be diagnosed?
- Personal history of symptoms
- Family history of ADPKD, ESRF, hypertension
- BP measurement -> BP may be raised
- Bloods - GFR test
- Ultrasound
- To look for cysts in the kidneys or other organs, such as the liver. - Screening / genetic testing
What value can be used as a prognostic marker for ADPKD?
TKV - total kidney volume.
Management of ADPKD.
- No treatment shown to slow disease progression
- Blood pressure control
- with ACE-inhibitor e.g. RAMIPRIL - Treat kidney stones and give analgesia
- Laparoscopic removal of cysts to help with pain/nephrectomy (remove
entire kidney) - Tolvaptan
- It can be used to slow down the growth of cysts, reducing overall kidney growth and preserving kidney function for longer.
But tolvaptan can only be used in adults who have:
1) CKD (stage 2 or 3) at the start of treatment
2) Evidence of rapidly progressing kidney disease - Children and siblings of patients with the disease should be offered
screening by renal ultrasound in their 20s - Avoid contact sports, NSAIDs, anti-coagulants
How does the epidemiology differ between ADPKD and ARPKD?
People with ADPKD normally present in middle age whereas people with ARPKD present in infancy.
What gene is mutated in autosomal recessive PKD?
- PKHD1 mutation on long arm (q) of chromosome 6
3 presentations of ARPKD?
At birth:
- Olighydramosis (lack of amniotic fluid)
Underdeveloped lungs – respiratory failure
Low ears, flat nasal bridge
Congenital liver fibrosis
Diagnosis of ARPKD.
- Diagnosed antenatally or neonatally
- Ultrasound - to see cysts
- CT & MRI to monitor liver disease
- Genetic testing
Management of ARPKD.
- Currently no treatment available
- Genetic counselling for family members
- Laparoscopic removal of cysts to help with pain/nephrectomy (remove
entire kidney) - Blood pressure control with ACE-inhibitor e.g. RAMIPRIL
- Treat stones and give analgesia
- Renal replacement therapy for ESRF
What diet is best for kidney disease?
Low potassium, phosphate, sodium, protein
