Renal - ADPKD

Question 1

describe the aetiology and pathophysiology of ADPKD

Answer 1

Autosomal dominant mutation in PKD1 (85%) or PKD2 gene… mutation in polycystin 1 or 2 (regulate tubular and vascular dev. in kidneys and other organs)… formation of cysts in cortex and medulla of kidneys and their enlargment, + extrarenal manifestations.

Question 2

describe the renal complications associated with ADPKD.

Answer 2

1. loin pain (most common Sx) - can be caused by renal haemorrhage, stones and UTIs, or chronic pain from stretching of renal capsule by cysts
2. HTN - compression of arterioles supplying nearby healthy nephrons results in nephron ischaemia and RAAS activation
3. UTI and pyelonephritis - due to compression of nearby collecting system and urinary stasis
4. renal stones - 2x more common, usually uric acid. same as aboce
5. frequency and nocturia - due to impaired urine concentrating capacity
6. bilateral kidney enlargement - may be palpable on abdo exam
7. gross haematuria following trauma (30-50%)
8. CKD - usually in 4th-6th decade

Question 3

describe possible extra-renal manifestations of ADPKD

Answer 3

1. polycystic liver disease (80%) - mostly asymptomatic but Sx can occur due to mass effect (e.g. dyspnoea, GORD, low back pain, obstructive jaundice) or from cyst complications (e.g. infection, torsion or rupture)
2. intracranial (berry) aneurysms
3. aneurysms and dissection elsewhere in vasculature (e.g. thoracic aorta, coronary artery)
4. subdural haematoma - increased risk due to arachnoid membrane cysts
5. cardiac abnormalities, e.g. mitral valve prolapse or aortic insufficiency with aortic root dilation
6. male infertility (rare) - due to cysts in seminal vesicles and defective sperm motility
7. pancreatitis (rare) - due to pancreatic cysts

Question 4

which investigations would you perform in someone with suspected ADPKD?

Answer 4

1. Bedside tests
   - urinalysis: check for infection, protein (microalbuminuria in 1.3) and haematuria
   - urine MCandS: coliforms most usual path.
2. Bloods
   - FBC: ?polycythaemia as polycystic kidneys can produce excess EPO
   - UandE, creatinine and eGFR: assess renal function
   - bone profile
3. Imaging
   - renal USS: can detect renal cysts from 1-1.5cm diameter. 100% sensitivity for PKD1 in >20 yrs, false negs can occur below this age. Can also scan other organs.
   - CT/MRI: more sensitive as can detect cysts >0.5 cm
4. Genetic testing

Question 5

how would you manage a pt with ADPKD?

Answer 5

Tx is supportive and nothing shown to slow or halt disease progression.

1. Monitoring
   - annual blood tests and USS if BP and bloods normal, more if not
2. Medical management
   - ACEi/ARBs if HTN
   - treat UTIs and renal stones as for normal pop.
   - renal pain: avoid nephrotoxic drugs (e.g. NSAIDs), involve pain team, USS-guided percutaneous drainage of large painful cysts
   - ESRD: dialysis/transplant