Polycystic Kidney Disease for USMLE Step 3
Polycystic Kidney Disease for the USMLE Step 3 Exam
- Definition:
- Polycystic kidney disease (PKD) is a genetic disorder characterized by the formation of numerous cysts in the kidneys, leading to progressive renal enlargement and dysfunction. The two primary forms are autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).
- Etiology:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD):
- The most common form, caused by mutations in the PKD1 gene (85% of cases) or the PKD2 gene (15%). ADPKD typically presents in adulthood.
- Autosomal Recessive Polycystic Kidney Disease (ARPKD):
- Less common, caused by mutations in the PKHD1 gene. It presents early in life, often in infancy, with significant kidney and liver involvement.
- Pathophysiology:
- Cyst Formation:
- Cysts in PKD form from the renal tubular epithelium due to abnormal cell proliferation and fluid secretion. These cysts progressively enlarge, compressing normal kidney parenchyma and leading to nephron loss.
- Progression to Renal Failure:
- In ADPKD, most patients develop chronic kidney disease (CKD) and eventually end-stage renal disease (ESRD), usually by the 5th or 6th decade of life. ARPKD often results in early renal failure.
- Extrarenal Manifestations:
- PKD affects other organs, with cysts commonly forming in the liver, pancreas, and spleen. Vascular complications, such as intracranial aneurysms, are a notable feature of ADPKD.
- Clinical Features:
- Autosomal Dominant Polycystic Kidney Disease (ADPKD):
- Renal Manifestations:
- Hypertension: One of the earliest manifestations, due to activation of the renin-angiotensin-aldosterone system (RAAS).
- Flank Pain: Caused by cyst growth, hemorrhage, or infection.
- Hematuria: May occur due to cyst rupture.
- Recurrent Urinary Tract Infections (UTIs): Infected cysts can lead to fever and bacteriuria.
- Nephrolithiasis: Kidney stones are common, often composed of calcium oxalate or uric acid.
- Progressive Renal Failure: Gradual decline in renal function, eventually leading to ESRD.
- Extrarenal Manifestations:
- Hepatic Cysts: Present in up to 80% of patients, often asymptomatic.
- Intracranial Aneurysms: Increased risk of subarachnoid hemorrhage, particularly in those with a family history of aneurysms.
- Mitral Valve Prolapse (MVP): Present in about 25% of ADPKD patients.
- Autosomal Recessive Polycystic Kidney Disease (ARPKD):
- Renal Manifestations: Presents early in life with enlarged, echogenic kidneys. Respiratory distress due to pulmonary hypoplasia is common in neonates.
- Hepatic Manifestations: Congenital hepatic fibrosis leading to portal hypertension is a hallmark of ARPKD.
- Diagnosis:
- Imaging:
- Ultrasound: The preferred initial imaging modality for detecting renal cysts. Diagnostic criteria depend on the number of cysts and the patient's age.
- CT or MRI: May be used for detecting smaller or complicated cysts.
- Genetic Testing:
- Identifies mutations in PKD1, PKD2, or PKHD1. It is useful when the diagnosis is uncertain or for family planning.
- Management:
- Blood Pressure Control:
- ACE inhibitors or ARBs are the first-line treatment for hypertension in ADPKD. They may slow disease progression.
- Pain Management:
- Pain from cyst enlargement can be treated with analgesics, cyst aspiration, or surgical intervention for refractory cases.
- Treatment of Infections:
- Antibiotics that penetrate cysts, such as fluoroquinolones or trimethoprim-sulfamethoxazole, are used for cyst infections.
- Renal Replacement Therapy (RRT):
- Patients with ESRD require dialysis or kidney transplantation. ADPKD patients generally do well post-transplant.
- Screening for Intracranial Aneurysms:
- Recommended in patients with a family history of aneurysms or personal risk factors, using magnetic resonance angiography (MRA).
Key Points
- Polycystic kidney disease is an inherited disorder causing cyst formation in the kidneys, leading to progressive renal failure.
- ADPKD is caused by mutations in PKD1 or PKD2, typically presenting in adulthood with hypertension, hematuria, and renal failure.
- ARPKD affects infants and children, with severe renal and hepatic complications.
- Diagnosis is based on imaging, primarily ultrasound, and genetic testing when necessary.
- Treatment focuses on controlling blood pressure, managing pain and infections, and providing renal replacement therapy for end-stage renal disease.
- Screening for intracranial aneurysms is recommended in high-risk ADPKD patients.