Epidemiology and Etiology
Polycystic kidney disease (PKD) affects about 500,000 people in the United States. One of the 2 main types of PKD is autosomal dominant polycystic kidney disease (ADPKD).
- Most commonly inherited kidney disease
- Prevalence: 1 in 1,000 live births
- Cause of CKD in 5% of annual dialysis initiation
- Decline in renal function often noted by the 4th decade of life
- Autosomal dominant (positive family history)
- Either a mutation of:
- PKD1 (encodes polycystin-1) on chromosome 16 OR
- PKD2 (encodes polycystin-2) on chromosome 4
The age of symptom onset is variable, but typically in adulthood. Patients with PKD1 mutation present with symptoms earlier than patients with PKD2.
- Kidney function impairment
- Flank or abdominal pain
- Enlarged, palpable kidneys on physical exam (patients with PKD1 mutation have larger kidneys and more cysts than patients with PKD2)
- Recurrent urinary tract infections (UTIs)
- Cerebral aneurysm:
- 4 times higher risk than the general population
- Can rupture with subarachnoid hemorrhage or intracerebral hemorrhage (ICH)
- The most serious risk factor associated with ADPKD
- Benign, asymptomatic hepatic cysts:
- Higher prevalence as age increases
- Can be complicated by cyst infection or hemorrhage
- Benign, asymptomatic pancreatic cysts
- Seminal vesicle cysts
- Cardiac valvular abnormalities:
- Most commonly mild mitral valve prolapse or aortic regurgitation
- Often asymptomatic with a mild murmur
- Colonic diverticula
- Abdominal wall and inguinal hernias
Diagnosis is made with the combination of positive family history and the presence of multiple, bilateral renal cysts.
- Assess for palpable kidneys.
- Assess for syndromic features and extrarenal manifestations.
- Ultrasonography of abdomen to detect renal cysts (1st line)
- CT or MRI:
- If ultrasound findings inconclusive
- Can detect cysts of smaller size
- Determines total kidney volume (helps assess the risk of kidney disease progression)
- If imaging tests uncertain
- If atypical features:
- Early, severe ADPKD
- Renal failure without significantly enlarged kidneys
- The disease is significantly discordant with family members.
- Significant asymmetry of disease between each kidney
- ADPKD without a family history
- If information is needed for reproductive counseling
Management and Prognosis
- To slow renal disease progression
- To control blood pressure and lower cardiovascular risk
- ACE inhibitors and ARBs for blood pressure control
- Restrict dietary sodium.
- Increase fluid intake.
- Manage complications (e.g., UTIs, nephrolithiasis).
- Tolvaptan for high-risk patients:
- Blocks the positive effect of vasopressin on cyst production
- Can decrease cyst growth
For end-stage renal disease (ESRD):
- Hemodialysis or peritoneal dialysis
- Kidney transplantation
- Benefits of genetic counseling and screening for patients and family:
- Information on diagnosis and prevention/treatment of complications
- Family planning (risks of passing condition to offspring)
- Possible kidney transplant donor among relatives
- Screening for intracerebral aneurysms with presymptomatic imaging (MRA or CT angiography):
- Family history of intracranial aneurysm
- Plans to have major surgery
- High-risk occupations (ruptured aneurysm could put other lives at risk, e.g., pilot)
- Requires anticoagulation (increased risk of bleeding)
- Varies from person to person
- Generally a slow rate of disease progression
- About ½ of patients ≥ 75 years of age require dialysis and/or kidney transplantation.
- Most patients die from cardiac causes.
- Particularly poor prognosis with a ruptured cerebral aneurysm
The 2 main types of polycystic kidney disease are ADPKD and autosomal recessive polycystic kidney disease (ARPKD).
|Inheritance||Autosomal dominant||Autosomal recessive|
|Genes involved||PKD1, PKD2||PKHD1|
|Associated proteins||Polycystin-1, polycystin-2||Fibrocystin|
|Age of presentation||Adulthood||Antenatal, neonatal, infant|
|Gross and pathologic morphology|
|Ultrasound findings|| Multiple cysts (based on age):|
ARPKD: autosomal recessive polycystic kidney disease
- Multiple benign simple cysts: Renal cysts are a common, asymptomatic, incidental finding in adults. The cysts increase in number with age. Differentiation from mild ADPKD may be difficult. Patients without ADPKD generally do not have a family history, gross hematuria, flank pain, or renal insufficiency.
- Localized renal cystic disease: a localized, benign condition confused with PKD. Unlike PKD, the condition is a localized cystic disease and neither bilateral nor progressive. Patients have no family history of ADPKD.
- Acquired renal cystic disease: chronic kidney disease is frequently associated with the development of multiple small cysts bilaterally. The cysts are often small (< 0.5 cm) and patients have no family history. The kidneys have a smooth contour and are small to normal in size. Associated extrarenal manifestations are not noted.
- Medullary sponge kidney: malformation of the collecting ducts (tubular dilatation) limited to the medullary pyramids. The condition may mimic PKD on urographic studies. Patients can present with kidney stones, hematuria, and UTIs. Unlike PKD, the renal cortex is spared, which can be seen on CT or MRI.
- Autosomal dominant tuberous sclerosis complex: multiple, bilateral kidney cysts. Other findings include renal angiomyolipomas, facial angiofibromas, hypomelanotic macules, and retinal nodular hamartomas. Diagnosis is based on clinical findings and genetic testing (TSC1 or TSC2 pathogenic mutation).
- Autosomal dominant tubulointerstitial kidney disease: a rare genetic disorder characterized by a gradual decline in kidney function from the teenage years. The onset of ESRD is variable. Presentation includes early-onset gout, hyperuricemia, and, in some, renal cysts. Unlike PKD, cysts are at the corticomedullary junction and the kidneys are small to normal in size.
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