Protocol for Diagnosis of ADPKD
Diagnostic Approach Based on Clinical Scenario
For adults with a positive family history, start with renal ultrasonography and apply age-specific diagnostic criteria; for children and young people, either immediate diagnostic screening or ongoing surveillance without diagnostic testing are equally valid approaches, with the decision made through shared decision-making with parents. 1, 2, 3
Adults with Positive Family History
First-Line Imaging: Renal Ultrasonography
Ultrasonography is the recommended initial diagnostic test for adults with a known family history of ADPKD. 2, 3
Age-Specific Ultrasound Diagnostic Criteria (PKD1/PKD2 Families):
Ages 15-39 years:
Ages 40-59 years:
- ≥2 cysts in each kidney = diagnosis confirmed
- ≤2 cysts total = diagnosis ruled out 2
Ages ≥60 years:
- ≥4 cysts in each kidney = diagnosis confirmed 2
When Ultrasound Results Are Equivocal or Atypical
Proceed to MRI or genetic testing when ultrasound findings are unclear or do not fit typical patterns. 2, 3
MRI Diagnostic Criteria:
- Ages 16-40 years with positive family history:
MRI provides 100% sensitivity and specificity in at-risk subjects aged 16-40 years using the >10 cyst criterion. 4
Children and Young People (<15 years)
Two Equally Valid Approaches
Parents should be offered counseling about two equally acceptable clinical pathways: 1
- Ongoing surveillance (monitoring for hypertension and proteinuria without diagnostic testing)
- Immediate diagnostic screening (ultrasonography or genetic testing)
The decision should involve shared decision-making between parents/guardians and healthcare professionals, with minors involved when possible. 1
If Diagnostic Screening Is Chosen: Ultrasonography
Renal ultrasonography is the current gold standard for radiological diagnosis in children due to smaller body size, no sedation requirement, and no radiation exposure. 1, 3
Interpretation in Children:
≥1 kidney cyst in at-risk child:
Multiple cysts with negative family history:
- Requires clinical work-up for other cystic kidney diseases
- Parental ultrasonography should be performed 1
Single cyst:
- Requires follow-up imaging
- May not be confirmed on repeat scan in rare cases 1
Normal ultrasound:
- Cannot rule out ADPKD in childhood due to gradual cyst appearance
- Negative predictive value is limited
- If rescreening is requested, intervals should not be shorter than 3 years 1
Common pitfall: A normal ultrasound in childhood does not exclude ADPKD, as cysts develop gradually and may not be detectable until later in life, especially in families with milder phenotypes. 1
Genetic Testing Indications
Strongly Recommended:
Offer genetic testing with multigene panels (not single-gene testing) in these scenarios: 1, 3
- Infants and children with very-early-onset symptomatic disease (independent of family history)
- Progressive disease (increasing cyst number or kidney volume) with negative family history
- Few kidney cysts with otherwise suggestive clinical picture
- Young living-related kidney donors at risk based on family history
- Equivocal or atypical imaging results
- Discordant imaging and glomerular filtration rate
- Variable intrafamilial disease severity
- Family planning and preimplantation diagnosis considerations 1, 2, 3
Multigene Panel Approach:
Use comprehensive cystic kidney disease panels rather than testing single ADPKD genes because unusual genetic constellations (biallelic mutations, contiguous gene deletions, HNF1B mutations) can radically alter phenotype and prognosis. 1, 3
Panels should include adequate coverage of PKD1, PKD2, PKHD1, DZIP1L, HNF1B, and genes for other ciliopathies (NPHP, BBS). 1
Not Recommended:
Do not perform genetic testing in patients with a single cyst, no extrarenal findings, and negative family history. 1
Adults with Incidental Cysts and No Family History
Perform kidney MRI or CT followed by genetic testing if imaging is atypical or equivocal. 3
This population requires more extensive work-up because the diagnosis cannot rely on family history-based criteria. 3
Important Diagnostic Caveats
Limitations of Ultrasound/MRI Criteria:
These imaging criteria apply ONLY to families with pathogenic PKD1 or PKD2 variants, not to those with minor gene variants or other cystic kidney diseases. 2, 3
Differential Diagnosis:
Several inherited diseases mimic ADPKD with kidney and/or liver cysts, including HNF1B-related kidney disease, Alagille syndrome, and COL4A-related diseases. 3
Genetic testing with multigene panels helps distinguish these conditions. 3
Disease Severity Variability:
ADPKD severity varies based on the causal gene (PKD1 vs PKD2), type of PKD1 mutation, sex, and environmental factors. 2
PKD1 mutations are associated with more severe disease and earlier onset of kidney failure compared to PKD2. 5, 6
Prognostic Assessment After Diagnosis
Use the Mayo Imaging Classification (MIC) to predict future kidney function decline and timing of kidney failure once ADPKD is confirmed. 2, 3, 7
Measure height-adjusted total kidney volume most accurately by MRI or CT using automated/semi-automated tools to stratify patients into risk categories (1A-1E). 2, 3