BACKGROUND
- Polycystic kidney diseases (PKD) are a leading cause of renal failure and common indication for dialysis or transplantation
- May arise sporadically as a developmental abnormality or acquired in adult life.
- Most forms of polycystic kidney disease are hereditary.
DEFINITION
- Inherited forms of PKD are due to germ-line mutations with Mendelian inheritance patterns.
- Inherited PKD includes:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- ADPKD type I- accounts for 85-90% of disease
- ADPKD type II
- Autosomal Recessive Polycystic Kidney Disease
- Nephronophtisis
- Medullary Cystic Kidney Disease
EPIDEMIOLOGY
- Autosomal Dominant Polycystic Kidney Disease is the most common form of PKD.
- Occurs in 1 in 800 live births with 4-6 million people afflicted worldwide.
- Disease is more common in Caucasians than African-Americans.
PATHOGENESIS & GENETICS
- ADPKD is an inherited form of PKD and approximately 85% of families with this disease have an abnormality on chromosome 16 at the PDK1 locus.
- ADPKD type I is caused by a mutation in the PKD1 gene which codes for the membrane receptor polycystin-1 on the renal tubular epithelium. This protein activates intracellular signaling pathways leading to proliferation and cyst formation.
- In addition, there is also persistent apoptosis of normal renal tubular cells thereby allowing for greater cystic epithelial proliferation.
- ADPKD type II is caused by a mutation I in the PKD2 gene which codes for polycystin-2 which I a calcium-permeable channel.
CLINICAL MANIFESTATIONS
- ADPKD type I tends to present earlier in life (patient in their 50s) but has a more progressive course and shorter life expectancy than type II disease.
- Chronic Abdominal pain or flank pain
- Acute exacerbation of pain can be indicative of cyst rupture or hemorrhage
- Hypertension: mediated by renin-angiotensin-aldosterone axis
- Hematuria
- Renal insufficiency
- Frequent UTIs in males
- Frequent nephrolithiasis...................
