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
