Polycystic Kidney Disease for USMLE Step 2
Polycystic Kidney Disease for the USMLE Step 2 Exam
- Definition:
- Polycystic kidney disease (PKD) is an inherited disorder where multiple fluid-filled cysts develop in the kidneys, causing progressive renal dysfunction. There are two major forms: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).
- Etiology:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD):
- The most common form, ADPKD is caused by mutations in the PKD1 gene (85% of cases) or the PKD2 gene (15%). PKD1 mutations are associated with more severe disease. ADPKD generally presents in adulthood.
- Autosomal Recessive Polycystic Kidney Disease (ARPKD):
- Caused by mutations in the PKHD1 gene, ARPKD presents in infancy or early childhood with both renal and hepatic involvement, often more severe than ADPKD.
- Pathophysiology:
- Cyst Formation:
- Cysts form from the renal tubular epithelium due to abnormal cell proliferation, fluid secretion, and altered cell-matrix interactions. Cyst growth compresses normal kidney tissue, leading to progressive nephron loss and eventual renal failure.
- Renal Failure:
- In ADPKD, most patients develop end-stage renal disease (ESRD) by their 50s or 60s. In ARPKD, renal failure often occurs in infancy or childhood.
- Extrarenal Manifestations:
- Cysts can also form in other organs, such as the liver, pancreas, and spleen. Vascular complications, such as intracranial aneurysms, are common in ADPKD.
- Clinical Features:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD):
- Hypertension: Frequently the first sign, due to renal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS).
- Flank Pain: Caused by cyst expansion, hemorrhage, or infection.
- Hematuria: May occur with cyst rupture or infection.
- Recurrent UTIs: Cyst infections cause fever, flank pain, and bacteriuria.
- Nephrolithiasis: Kidney stones are common, often composed of uric acid or calcium oxalate.
- Renal Failure: Gradual decline in renal function, leading to ESRD.
- Extrarenal Manifestations:
- Hepatic Cysts: Common in ADPKD, especially in women.
- Intracranial Aneurysms: Occur in about 10% of ADPKD patients, increasing the risk of subarachnoid hemorrhage.
- Mitral Valve Prolapse (MVP): Present in about 25% of ADPKD patients.
- Autosomal Recessive Polycystic Kidney Disease (ARPKD):
- Presents in infancy with enlarged, echogenic kidneys. Respiratory distress due to pulmonary hypoplasia is common in neonates.
- Liver Disease: Congenital hepatic fibrosis leading to portal hypertension and hepatosplenomegaly.
- Diagnosis:
- Imaging:
- Ultrasound: The first-line diagnostic tool for detecting multiple renal cysts. Diagnostic criteria depend on age and the number of cysts.
- CT or MRI: Can detect smaller or complicated cysts.
- Genetic Testing:
- Confirms mutations in PKD1, PKD2, or PKHD1, useful in ambiguous cases or for family planning.
- Management:
- Blood Pressure Control:
- ACE inhibitors or ARBs are the first-line treatment for hypertension in ADPKD and may slow disease progression.
- Pain Management:
- Analgesics are used for flank pain, with cyst aspiration or surgery for refractory cases.
- Treatment of Infections:
- Fluoroquinolones or trimethoprim-sulfamethoxazole are used to treat cyst infections.
- Management of Kidney Stones:
- Hydration and urine alkalinization are recommended. Larger stones may require surgical intervention or lithotripsy.
- Renal Replacement Therapy:
- ESRD is managed with dialysis or kidney transplantation, with good outcomes in ADPKD patients.
- Screening for Intracranial Aneurysms:
- Screening is recommended for patients with a family history of aneurysms or personal risk factors, using magnetic resonance angiography (MRA).
Key Points
- Polycystic kidney disease (PKD) is an inherited disorder leading to renal cyst formation and progressive renal failure.
- ADPKD is caused by mutations in PKD1 or PKD2 and presents in adulthood with hypertension, hematuria, recurrent UTIs, and renal failure.
- ARPKD affects infants and children with severe renal and hepatic involvement.
- Diagnosis is made using imaging (ultrasound) and genetic testing if needed.
- Treatment focuses on blood pressure control, managing cyst-related complications, and providing renal replacement therapy for ESRD.
- Screening for intracranial aneurysms is recommended in high-risk ADPKD patients.