Polycystic Kidney Disease (PKD)

Overview

• PKD is a genetic disease leading to the formation of cysts in the kidneys.
• Cysts are fluid-filled sacs that cause kidneys to enlarge and become dysfunctional over time.
• Cysts develop in both the outer (cortex) and inner (medulla) layers of the kidneys.

Pathophysiology

• Cysts lined with renal tubular epithelium fill with fluid, increasing in size over time.
• Growing cysts can compress blood vessels, starving surrounding healthy nephrons of oxygen.
• Poorly perfused kidneys activate the renin-angiotensin-aldosterone system, leading to fluid retention and hypertension.
• Expanding cysts can compress the urinary collecting system, leading to urinary stasis and potential kidney stones.
• Destruction of normal renal architecture can cause flank pain and hematuria (blood in urine).
• Over time, affected nephrons lead to renal insufficiency and eventual renal failure.

Types of PKD

Autosomal Dominant PKD (ADPKD)

• Previously known as adult PKD; symptoms typically manifest in adulthood.
• Genes Involved:
  • PKD1: Mutation leads to a more severe and earlier onset.
  • PKD2: Mutation results in a milder form and later onset.
• Proteins:
  • Polycystin-1 (PC1) and Polycystin-2 (PC2) are integral to the primary cilia of nephron cells.
• Function of Primary Cilia:
  • Responds to fluid flow, allowing calcium influx which inhibits cell proliferation.
• Cyst Formation:
  • Loss of normal signaling leads to abnormal cell proliferation and cyst enlargement.
• Inheritance:
  • Affected individuals inherit one mutated gene (heterozygous), but a second mutation occurs in kidney tubular cells, causing cyst formation.
• Associated Conditions:
  • Cysts may also develop in the liver, pancreas, and seminal vesicles.
  • Vascular complications include aortic root dilation and Berry aneurysms, increasing the risk of heart failure and subarachnoid hemorrhage.

Autosomal Recessive PKD (ARPKD)

• Previously referred to as infantile PKD; symptoms usually present in infancy or even before birth.
• Genetic Basis:
  • Involves mutations on both copies of the PKD1 gene that codes for fibrocystin.
• Mechanism:
  • Similar to ADPKD, but cyst formation can lead to renal failure before birth.
• Fetal Complications:
  • Oligohydramnios (low amniotic fluid) can lead to Potter sequence, causing developmental abnormalities (e.g., club feet, flattened nose) and pulmonary hypoplasia (underdeveloped lungs).
• Diagnosis:
  • Detected via prenatal ultrasound showing large kidneys with cysts and oligohydramnios.
  • Congenital hepatic fibrosis may lead to portal hypertension, causing complications like esophageal varices and splenomegaly.

Treatment

• Focused on managing specific symptoms and organ dysfunction:
  • Hypertension:
    • ACE inhibitors or Angiotensin receptor blockers to counteract the renin-angiotensin-aldosterone system.
  • Cysts:
    • Ursodeoxycholic acid (ursodiol) may slow cholesterol absorption.
  • Kidney Failure:
    • Dialysis or kidney transplant may be necessary.
  • Portal Hypertension:
    • Consider a portacaval shunt or liver transplant.

Summary

• PKD is a genetic disorder characterized by cyst formation in the kidneys, leading to enlargement and failure.
• Two main types: ADPKD (manifests in adulthood) and ARPKD (manifests in infancy).
• Understanding and managing this disease is crucial for current and future clinicians.