What are the diagnostic criteria for Autosomal Dominant Polycystic Kidney Disease (ADPKD)?

Diagnostic Criteria for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

For adults with a positive family history of ADPKD, begin with renal ultrasonography and apply age-specific cyst thresholds: ≥3 total kidney cysts (ages 15-39), ≥2 cysts in each kidney (ages 40-59), or ≥4 cysts in each kidney (ages ≥60) to confirm diagnosis. 1

Ultrasound Diagnostic Criteria by Age (Positive Family History)

The diagnostic approach differs substantially based on patient age, as cyst burden increases over time:

Ages 15-39 Years

• Diagnosis confirmed: ≥3 total kidney cysts (both kidneys combined) 1, 2
• Diagnosis ruled out: ≤1 kidney cyst total 1, 2

Ages 40-59 Years

• Diagnosis confirmed: ≥2 cysts in each kidney 1, 2
• Diagnosis ruled out: ≤2 cysts total 1, 2

Ages ≥60 Years

• Diagnosis confirmed: ≥4 cysts in each kidney 1, 2

Children <15 Years

• Highly suggestive: ≥1 kidney cyst on ultrasound (89% specificity <5 years, 100% specificity >5 years) 3, 4

Critical caveat: These ultrasound and MRI criteria apply only to families with pathogenic variants of PKD1 or PKD2, not to minor gene variants. 1, 2

MRI Diagnostic Criteria (Ages 16-40 Years)

When ultrasound is equivocal or greater sensitivity is needed:

• Diagnosis confirmed: >10 total kidney cysts 1, 2
• Diagnosis ruled out: <5 total kidney cysts 1, 2
• MRI has greater sensitivity for detecting smaller cysts compared to ultrasound 1
• CT with or without contrast can also be used as an alternative to MRI 1

Diagnostic Algorithm

For Adults WITH Known Family History

1. Start with abdominal ultrasound as first-line imaging 1, 2
2. Apply age-specific ultrasound criteria as outlined above 1
3. If equivocal or atypical findings: Proceed to MRI or genetic testing 1, 3
4. In genetically resolved families: Targeted genetic testing for the specific family variant is usually sufficient 1

For Adults WITHOUT Known Family History (Incidental Cysts)

When kidney and/or liver cysts are detected incidentally:

• If few cysts with normal kidney function/size and no extrarenal features: Proceed to kidney MRI (or CT) 1
• If multiple cysts, discordant imaging/GFR, or atypical renal/extrarenal findings: Proceed directly to genetic testing 1
• If MRI and genetics remain equivocal: Consider future imaging/genetic follow-up in approximately 2 years 1

Genetic Testing Indications

Genetic testing is particularly valuable and should be strongly considered in these specific scenarios: 1, 3, 4

• Few kidney cysts present with otherwise suggestive clinical picture 1, 3
• Variable intrafamilial disease severity, including very-early-onset ADPKD 1, 3
• Discordant imaging and glomerular filtration rate 1, 3
• Negative or indeterminate family history 1, 3
• Young (aged <30 years) living-related kidney donors at risk based on family history 1, 3
• Family planning and preimplantation diagnosis considerations 1, 3
• Infants and children with very-early-onset symptomatic disease 3, 4

Use comprehensive multigene cystic kidney disease panels rather than testing single ADPKD genes (PKD1/PKD2 only), as unusual genetic constellations can radically alter phenotype and prognosis. 3, 4 Whole-genome sequencing with targeted analysis to a polycystic kidney disease gene panel achieves 100% sensitivity and specificity for germline variants, with an overall diagnostic rate of 70% in unselected cohorts (81% in typical ADPKD, 60% in atypical presentations). 5

Important Diagnostic Pitfalls

Mimicking Conditions

Several inherited diseases may mimic ADPKD with kidney and/or liver cysts, including HNF1B-related kidney disease, Alagille syndrome, COL4A-related diseases, and PKHD1-related disorders. 1, 4 In atypical presentations, 44% of genetic diagnoses involve genes other than PKD1/PKD2. 5

Genotype-Phenotype Considerations

• PKD1 mutations: More severe disease with larger kidneys and earlier ESRD (approximately 15 years earlier than PKD2) 1
• PKD2 mutations: Milder phenotype that may present later in life; use of PKD1 diagnostic criteria may lead to false-negative results in younger PKD2 patients 1
• Truncating PKD1 mutations: More severe than nontruncating mutations 1
• Male sex, obesity, and high salt intake: Associated with more severe disease 1

Donor Evaluation Specifics

For prospective living kidney donors with family history:

• Ages >30 years: Safe to proceed if ultrasound or CT shows no cysts 1
• Ages 20-30 years: Negative ultrasound does NOT rule out ADPKD; genetic testing recommended 1
• Donation contraindicated if: 2-3 cysts in each kidney, or complex/septated cysts present 1

Prognostic Assessment After Diagnosis

Once ADPKD is confirmed, employ the Mayo Imaging Classification (MIC) to predict future kidney function decline and timing of kidney failure. 1, 3

• MIC divides ADPKD into: Typical (class 1) and atypical (class 2) presentations 1
• Prognostic information is valid only for class 1 patients with typical imaging findings 1
• Measure height-adjusted total kidney volume most accurately by MRI or CT using automated/semi-automated tools 1, 3
• Stratifies patients into 5 risk groups (1A-1E) indicating accelerating decline in kidney function 1, 3