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Polycystic Kidney Disease for USMLE Step 1

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Polycystic Kidney Disease
  • Definition:
    • Polycystic kidney disease (PKD) is an inherited disorder characterized by the formation of fluid-filled cysts in the kidneys, leading to progressive renal enlargement and dysfunction. There are two forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).
  • Etiology:
    • Autosomal Dominant Polycystic Kidney Disease (ADPKD):
    • ADPKD is caused by mutations in the PKD1 gene (85% of cases) or the PKD2 gene (15%). Mutations in PKD1 tend to cause more severe disease. ADPKD typically manifests in adulthood.
    • Autosomal Recessive Polycystic Kidney Disease (ARPKD):
    • Caused by mutations in the PKHD1 gene, which encodes fibrocystin. ARPKD presents in infancy or childhood with more severe renal and hepatic involvement.
  • Pathophysiology:
    • Cyst Formation:
    • Cysts in PKD develop from renal tubular epithelial cells due to abnormal proliferation, fluid secretion, and altered cell-matrix interactions. These cysts grow over time, compressing surrounding kidney tissue and leading to loss of nephrons.
renal cyst formation
    • Progression to Renal Failure:
    • As cysts enlarge, they cause fibrosis, ischemia, and eventual loss of kidney function. Most ADPKD patients develop end-stage renal disease (ESRD) by their 50s or 60s.
    • Extrarenal Manifestations:
    • PKD is a systemic disorder, and cysts can also occur in the liver, pancreas, and spleen. Vascular abnormalities, such as intracranial aneurysms, are common in ADPKD.
  • Clinical Features:
    • Autosomal Dominant Polycystic Kidney Disease (ADPKD):
    • Renal Manifestations:
    • Hypertension: The earliest and most common symptom, resulting from renal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS).
    • Flank Pain: Caused by cyst growth, hemorrhage, or infection.
    • Hematuria: May occur with cyst rupture or infection.
    • Recurrent Urinary Tract Infections (UTIs): Infected cysts can lead to fever, flank pain, and bacteriuria.
    • Nephrolithiasis: Kidney stones are common, often composed of uric acid or calcium oxalate.
    • Progressive Renal Failure: Most patients experience a slow decline in kidney function, eventually progressing to ESRD.
    • Extrarenal Manifestations:
    • Hepatic Cysts: Common, especially in women, usually asymptomatic but may cause hepatomegaly.
    • Intracranial Aneurysms: Increased risk of subarachnoid hemorrhage, particularly in patients with a family history of aneurysms.
    • Mitral Valve Prolapse (MVP): Seen in about 25% of patients, though usually asymptomatic.
    • Colonic Diverticula: Increased risk of diverticular disease.
    • Autosomal Recessive Polycystic Kidney Disease (ARPKD):
    • Typically presents in infancy with enlarged, echogenic kidneys. Newborns may have severe renal insufficiency or respiratory distress due to pulmonary hypoplasia (from oligohydramnios).
    • Liver Disease: Congenital hepatic fibrosis and portal hypertension are common and may dominate the clinical picture.
  • Diagnosis:
    • Imaging:
    • Ultrasound: The first-line imaging modality, showing numerous bilateral renal cysts. Diagnostic criteria depend on the number of cysts and patient age.
    • CT or MRI: Can be used to detect smaller cysts or confirm diagnosis when ultrasound findings are unclear.
    • Genetic Testing:
    • Confirmatory testing for PKD1, PKD2, or PKHD1 mutations can be done when clinical or imaging findings are uncertain, or for family planning purposes.
  • Management:
    • Blood Pressure Control:
    • ACE inhibitors or ARBs are the first-line treatment for hypertension in ADPKD, as they reduce intraglomerular pressure and slow the progression of kidney disease.
    • Pain Management:
    • Flank pain due to cysts can be treated with analgesics, cyst aspiration, or surgery for refractory cases.
    • Treatment of Infections:
    • Antibiotics that penetrate cysts, such as fluoroquinolones or trimethoprim-sulfamethoxazole, are used for cyst infections.
    • Management of Kidney Stones:
    • Adequate hydration and urine alkalinization can help prevent stone formation. Surgical intervention or lithotripsy may be needed for large stones.
    • Renal Replacement Therapy:
    • ESRD is managed with dialysis or kidney transplantation, which has outcomes similar to those of other causes of ESRD.
    • Screening for Intracranial Aneurysms:
    • Recommended for ADPKD patients with a family history of aneurysms or personal risk factors. Magnetic resonance angiography (MRA) is the preferred screening method.
Key Points
  • Polycystic kidney disease is an inherited disorder characterized by the formation of multiple renal cysts, leading to progressive kidney damage.
  • ADPKD is the more common form, caused by mutations in PKD1 or PKD2 genes, and typically presents in adulthood with hypertension, hematuria, and renal failure.
  • ARPKD affects infants and children, with severe renal and hepatic involvement.
  • Diagnosis is based on imaging (ultrasound) and genetic testing if needed. ADPKD diagnostic criteria depend on the number of cysts and patient age.
  • Management focuses on controlling hypertension (ACE inhibitors/ARBs), managing cyst-related complications, and providing renal replacement therapy when necessary.
  • Screening for intracranial aneurysms is recommended in high-risk ADPKD patients.

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