Polycystic kidney disease

Question 1

Autosomal dominant polycystic kidney disease : Pathophysiology

Answer 1

1. Genetic disease that results in cysts developing in the cortex and medulla of the kidneys, this makes the kidneys larger than normal
2. Cysts compress the nephrons causing ischaemia and cause urinary stasis resulting in kidney stones
3. RAAS is activated leading to fluid retention and hypertension

Eventually deterioration of nephrons leads to renal failure

Question 2

ADPKD : Genetic pathophysiology

Answer 2

PKD1 or PKD2 : Inherited a single, heterozygous mutation
* The remaining functional copy of the gene is sufficient to produce the polycystin to prevent cyst formation
* As kidney develops, the random mutation in the 2nd copy of the gene is most guaranteed, resulting in cyst formation.

Question 3

ADPKD : Genetic types

Answer 3

1. ADPKD type 1
   * Polycystin -1 gene on Chr 16 - mutations results in more severe and earlier on set of renal failure
2. ADPKD type 2
   * Polycystin-2 gene on Chr 4 - mutations results in less severe and later onset of disease

Question 4

ADPKD : Clinical features

Answer 4

• Hypertension 2nd to RAAS activation
• Renal impairment
• Flank pain
• Haemauria
• Palpable kidneys
• Urinary stasis ; Recurrent UTI, Renal impairment

Question 5

ADPKD : Extra-renal manifestation

Answer 5

• Liver cysts : most common extra-renal manifestation, may cause hepatomegaly + total hypertension
• Berry aneurysms : rupture can cause subarachnoid haemorrhage within the circle of Willis
• CVS system : mitral valve prolapse, aortic root dilation + dissection of the aorta
• Other organ cysts include ; Panaceas, Spleen

Question 6

ADPKD : Investigation

Answer 6

Screening via Abdominal ultrasound

Question 7

ADPKD : Management

Answer 7

Tolvaptan (Vasopressin receptor 2 antagonist) recommended by NICE to treat ADPKD in adults to slow the progression of cyst development and renal insufficiency only if;
* CKD stage 2-3 at start of treatment
* Evidence of rapidly progressing disease

Question 8

Autosomal recessive polycystic kidney disease - Pathophysiology

Answer 8

-Much less common than ADPKD
* Due to defect in gene on chromosome 6 which encodes for fibrocystin - a protein important for normal renal tubule development

Question 9

Autosomal recessive polycystic kidney disease - Diagnosis

Answer 9

• Diagnosis : Prenatal US or early infancy with abdominal mass or renal failure, may present with potter’s syndrome secondary to oligohydramnios.
• End stage renal failure develops in childhood