Polycystic Kidney Disease Flashcards
Define polycystic kidney disease
PKD is part of a heterogeneous group of disorders characterised by renal cysts and numerous systemic and extrarenal manifestations
Autosomal-dominant polycystic kidney disease (ADPKD) is the more common form.
Explain the aetiology of nephrotic syndrome
Two genes have been identified in autosomal-dominant PKD (ADPKD):
- PKD1 - 85% of cases, encodes protein polycystin 1
- PKD2- 15% of cases and encodes polycystin 2
Polycystin is a membrane-bound multidomain protein involved in cell-cell and cell-matrix interactions
The genes develop an inactivating somatic mutation in a minority of cells, leading to loss of polycystin function and clonal cyst development
Explain the epidemiology of PKD
- Occurs worldwide and in all races
- MOST COMMON inherited kidney disorder
- Responsible for 10% of end-stage renal failure
- Autosomal-recessive PKD is far less common
Explain the cyst aetiology in PKD
Proliferative/hyperplastic abnormality of the tubular epithelium
- Early on, the cysts are connected to the tubules from which they arise and the fluid content is glomerular filtrate
- When cyst diameter >2 mm, they detach from the tubule and the fluid content is derived from secretion of the lining epithelium
- With time, the cysts enlarge and cause progressive damage to adjacent functioning nephrons- why onset is usually in 30s/40s as the cysts need time to grow
State some extra-renal manifestations of PCKD
1: Cysts in other organs than the kidney:
- liver: 94%
- seminal vesicle: 40%
- pancreas: 9%
- arachnoid membrane: 8% (→SAH)
2: Connective tissue abnormalities:
- mitral valve prolapse: 25%
- intracranial aneurysms: 8%
- abdominal hernia: 10%
Recognise the presenting symptoms of polycystic kidney disease
- Present at 30-40 yrs
- 20% have no family history
- May be asymptomatic
Family history may include ADPKD, ESRD, intracranial aneurysm, haemorrhagic stroke, or subarachnoid haemorrhage.
Common presenting symptoms include:
- flank/abdominal pain- may result from cyst enlargement/bleeding, stone, blood clot migration, infection
- renal colic
- gross haematuria
- cystitis occurs in 75% PKD PTs at some point: dysuria, urgency, suprapubic pain, fever
- headaches (less common, due to hypertension)
- Associated with berry aneurysms and may present with subarachnoid haemorrhage
Recognise the signs of PKD on physical examination
-
Abdominal distension-
- due to abdominal hernia or rectus abdominis diastasis
- also due to …
- Enlarged cystic kidneys - palpable renal or hepatic mass
- Hypertension (detection of HPTN is the commonest cause of diagnosis in 20-34yr olds)
Signs of extrarenal manifestations:
- Signs or symptoms of renal insufficiency/ESRD
- Signs of associated AAA or aortic valve disease
-
Cardiac murmur may be present, suggestive of:
- mitral valve prolapse
- mitral regurgitation
- aortic regurgitation
- dilated aortic root.
Identify appropriate investigations for polycystic kidney disease
- 1st line: renal USS performed when diagnosis is suspected
- CT/ MRI abdo/pelvis if USS doesnt meet diagnostic criteria, especially in patients with PKD2 mutations <30 years of age.
- Urinalysis/Gram stain and urine culture- detects presence of increased urinary albumin excretion or proteinuria (progression to CKD and LVH)
- Serum electrolytes, urea, creatinine
- Fasting lipid profile- elevated LDL/decreased HDl –> increased risk of renal insufficency
- ECG- cardiac murmurs or suspected left ventricular dysfunction
- Genetic testing (linkage analysis or gene sequencing) should be considered when imaging studies are inconclusive, to confirm a presumed diagnosis in the absence of family history of the disease
What are the diagnostic screening parameters for PKD?
USS:
- <30yrs: at least 2 unilateral or bilateral cysts
- 30-59yrs: 2 cysts in each kidney
- >60 years of age: 4 cysts in each kidney
- Absence of FHx: >10 cysts in each kidney
- Large echogenic kidneys (without distinct macroscopic cysts) in a child at 50% risk for the disease are diagnostic.
