polycystic kidney disease

see also:

• renal medicine (nephrology)
• Vic Better health Channel - polycystic kidney disease

• autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans affecting ~ 0.1% of the population, but does not usually present until middle age
• it is one of the ciliopathies
• 2 main autosomal dominant genetic causes but with wide clinical variability even within families:
  • PKD1 codes for polycystin 1 and is located on 16p13.3 and accounts for most ADPKD cases and is the more severe form with mean age of end stage renal disease (ESRD) for patients with ADPKD1 is 53 years
  • PKD2 codes for polycystin 2 is located on 4q21-q22 and accounts for 15% of ADPKD cases with mean age of ESRD for patients with ADPKD1 is 74 years
• the most frequent genetic cause of renal failure in adults and accounts for 6-8% of patients on dialysis
  • 70% of patients with ADPKD develop renal insufficiency if they survive to age 65 years
• clinical features usually begin in the third to fourth decade of life but some may have cysts in utero.
• it appears that an additional renal insult is needed to spur development of the cysts such as urolithiasis / renal stones / renal calculi:
  • when there are crystals forming within the kidney, the mTOR and the Src/STAT3 signaling pathways become active, leading to the prompt dilation of the affected renal tubule along the whole length up to and including the collecting duct, and, in people with ADPKD, this activation appears to be the trigger that initiates renal cyst development ¹⁾
• diagnosis cannot be reliably excluded until at least age 50yrs or so when absence of renal cysts is highly suggestive the patient does not have this condition.
• animal models implicate argipressin (vasopressin / ADH) as promoter of kidney cyst cell proliferation and luminal fluid secretion, hence a trial of the vasopressin antagonist, tolvaptan, was undertaken and appears to show substantial benefit, although 25% discontinued Rx due to adverse effects.

• autosomal recessive polycystic kidney disease (ARPKD)
• the most common heritable cystic renal disease occurring in infancy and childhood.

• see renal masses and cysts

• PKD1 genotype
• large kidneys
• several episodes of gross hematuria
• severe and frequent kidney infections
• hypertension
• multiple pregnancies
• black racial background

• may cause flank pain due to either:
  • enlarging cysts
  • bleeding within the cyst or a perinephric bleed
  • frank haematuria
  • infection of cysts, acute pyelonephritis, or urinary tract infections (UTIs) / cystitis
  • renal colic due to stones or blood clots
  • rarely, a coincidental hypernephroma
• an associated polycystic liver may cause a dull ache
• chronic renal failure is common
• those on dialysis are prone to diverticulitis
• increased risk of:
  • intracranial aneurysms
  • thoracic aortic dissections
  • aortic root dilatation
  • dolichoectasia
  • coronary artery dissections
  • cervical artery dissection (ie. internal carotid or vertebral arteries) ²⁾