How to diagnose Autosomal Dominant Polycystic Kidney Disease (ADPKD) using radiology in patients without a family history?

Diagnosing ADPKD with Radiology in Patients Without Family History

In patients without a family history of ADPKD who have incidentally detected kidney and/or liver cysts, start with kidney MRI (or CT with/without contrast), and if imaging shows >10 total kidney cysts in patients aged 16-40 years, ADPKD is confirmed; if imaging is equivocal or shows <5 cysts, proceed to genetic testing with a multigene panel. 1

Initial Imaging Approach

Begin with kidney MRI as the primary diagnostic modality in adults with incidentally detected cysts but no known family history. 1 CT with or without contrast is an acceptable alternative if MRI is unavailable or contraindicated. 1

MRI Diagnostic Thresholds for Ages 16-40 Years

• >10 total kidney cysts = ADPKD diagnosis confirmed 1, 2
• <5 total kidney cysts = ADPKD diagnosis excluded 1, 2
• 5-10 cysts = equivocal, proceed to genetic testing 1

These MRI criteria provide 100% sensitivity and 100% specificity in patients aged 16-40 years when compared to molecular testing. 3

When Imaging is Equivocal or Atypical

Proceed immediately to comprehensive genetic testing with a multigene panel rather than single-gene analysis when: 1, 4

• MRI shows 5-10 cysts (equivocal range) 1
• Few kidney cysts present but clinical picture otherwise suggestive 1, 4, 5
• Imaging findings are atypical (asymmetric or focal cystic disease) 1, 6
• Discordance between imaging findings and kidney function 1, 4, 5

Genetic Testing Strategy

Use multigene panels covering PKD1, PKD2, and other cystic kidney disease genes (including HNF1B, PKHD1, GANAB, TSC1/TSC2, and others) rather than testing single ADPKD genes. 1, 4, 5 This approach is critical because:

• 10-25% of ADPKD cases lack apparent family history due to de novo mutations, germline/somatic mosaicism, or mild parental disease from hypomorphic mutations 6
• Multiple inherited disorders mimic ADPKD with kidney and/or liver cysts, including HNF1B-related kidney disease, Alagille syndrome, tuberous sclerosis complex, and autosomal recessive polycystic kidney disease 1
• Unusual genetic constellations (biallelic mutations, contiguous gene deletions) can radically alter phenotype and prognosis 1, 4

Critical Diagnostic Pitfalls

Standard ultrasound and MRI criteria apply ONLY to PKD1 and PKD2 mutations, not to minor gene variants. 1, 2 If genetic testing reveals mutations in genes other than PKD1/PKD2, the imaging thresholds above are invalid. 1

Atypical imaging patterns require heightened suspicion for alternative diagnoses or unusual genetic mechanisms: 6

• Asymmetric or focal PKD may indicate somatic mosaicism 6
• Focal PKD without identified PKD1/PKD2 mutations suggests alternative genetic causes (GANAB, other minor genes) 6, 7
• Very-early-onset or rapidly progressive disease suggests biallelic mutations or contiguous gene deletion syndromes 1

Follow-Up Strategy

If both MRI and genetic testing remain equivocal or negative, repeat imaging and consider repeat genetic evaluation in approximately 2 years to monitor for cyst development or progression. 1 This approach accounts for the focal and sporadic nature of cyst development in ADPKD. 8

Special Considerations for Young Potential Living Donors

**For individuals aged <30 years being evaluated as potential living-related kidney donors with no family history but incidental cysts detected, genetic testing is particularly valuable** even if imaging shows few cysts. 1, 4 The combination of MRI (>10 cysts diagnostic, <5 cysts exclusionary) and comprehensive genetic testing provides the highest diagnostic certainty in this high-stakes clinical scenario. 3