Polycystic kidney disease (PKD) is an inherited disorder of the kidneys in which there is enlargement of the kidneys due to multiple cyst formation which causes irreversible damage to the kidneys.
There are 2 main forms of PKD:
- Autosomal dominant PKD (ADPKD) - more common and more severe in its manifestation in the kidneys. Affects 1 in 1000 approximately.
- Autosomal recessive PKD (ARPKD) - less common (1 in 20,000) but more severe in its manifestation outside of the kidney. It is associated with underdevelopment of the lungs (leading to breathing difficulties) as well as hepatic manifestations of the disease as well. 1/3rd of ARPKD babies will die in the first 4 weeks of life due to respiratory issues.
Pathophysiology
There are 3 main genes that are involved, those being PKD1 (85%) on chromosome 16 and PKD2 on chromosome 4 (encoding for polycystin-1 and polycystin-2 proteins). The third gene implicated is PKHD-1 on chromosome 4 which is associated with ARPKD
Mutations of these genes leads to defected cilia-mediated signalling on the surface lining the lumen of the tubules. This then triggers cystogenesis and cyst expansion.
As these cysts expand, they compress the parenchyma of the kidney as well as the local vascular urge → decreased GFR → RAAS activation → hypertension.
As time progresses, the kidneys become enlarged and scarred. This leads to irreversible damage and deterioration of renal function (CKD).
- ARPKD babies die within the first few hours of birth due to respiratory distress. It may also cause cystogenesis in the liver (with PKHD-1 mutation) which can lead to hepatic fibrosis later on. Cysts form only within the collecting ducts and not in the rest of the nephron, the baby is born with cysts already formed.
- ADPKD babies are born with normal kidneys but develop cysts between 30-60 years old unlike in ARPKD. The cysts vary from a fem millimetres to a few centimetres. These cysts may become purulent if infected or may even rupture
😷 Presentation
- Flank pain (in their 40s - 60s especially)
- Haematuria - classic presentation of a ruptured cyst.
- Cyst infection - presenting with flank pain, fever, dysuria, increased frequency.
- Hypertension - present in 2/3rds of patients.
- Renal failure - about 50% have end-stage renal disease.
- Nephrolithiasis - due to increased urinary stasis.
- Extra-renal cysts - especially in the liver (70%), pancreas, spleen, thyroid and seminal vesicles.
- Berry aneurysms - at the junction of the ACA and anterior communicating artery.
- Valvular disease - 25% of patients develop mitral valve prolapse.
- Diverticular disease
- Hernias
- Early satiety, dyspnoea lower back pain, abdominal fullness/bloating - due to the compression of the large kidneys on the surrounding organs.
🔍 Investigations
- USS - this is the modality of choice. We will discuss the criteria for diagnosis below as it differs with age, as the number of cysts increase with age.
- CT and MRI are useful to determine extra-renal manifestations of the disease.
🧰 Management
- Select patients may respond to tolvaptan which is a vasopressin receptor 2 antagonist. This helps slow the progression of cystogenesis and renal insufficiency if they have:
- CKD stage 2 or 3 when commencing treatment
- Rapidly progressed disease
Other management aspects include:
- Increasing water intake - 3-4 litres per day if the eGFR is >30ml/min.
- Hypertension management - target is <130/80mmHg
- CKD management
🚨 Complications
- Cyst rupture
- Cyst infection
- CKD
- Subarachnoid haemorrhage due to aneurysm rupture.
- Intracerebral haemorrhage due to hypertension