What marker is used to diagnose polycystic kidney disease?

Diagnostic Markers for Polycystic Kidney Disease

The primary markers used to diagnose polycystic kidney disease are imaging-based cyst counts on ultrasound, MRI, or CT, with genetic testing of PKD1 and PKD2 genes serving as the definitive molecular marker when imaging is equivocal or in atypical presentations. 1, 2, 3

Imaging Markers (First-Line Approach)

Ultrasound Cyst Criteria by Age

For adults with a positive family history, ultrasound is the first-line diagnostic marker, applying age-specific cyst thresholds: 2, 3

• Ages 15-39 years: ≥3 total kidney cysts (both kidneys combined) confirms diagnosis; ≤1 cyst rules out ADPKD 2, 3
• Ages 40-59 years: ≥2 cysts in each kidney confirms diagnosis; ≤2 total cysts rules out ADPKD 2, 3
• Ages ≥60 years: ≥4 cysts in each kidney confirms diagnosis 2, 3

Pediatric Ultrasound Markers

In children <15 years with known family history, ≥1 renal cyst on ultrasound is highly suggestive of ADPKD, with 89% specificity under age 5 and 100% specificity over age 5. 2, 3

• In fetuses/neonates with positive family history, hyperechogenic kidneys and/or kidneys enlarged >2 standard deviations are indicative markers 2
• A single cyst should not be considered definitive proof, as rare cases fail confirmation on follow-up 1, 2

MRI Cyst Criteria

For individuals aged 16-40 years with positive family history, MRI provides more sensitive cyst detection: 1, 2

• >10 total kidney cysts on MRI confirms ADPKD 1, 2
• <5 total cysts rules out ADPKD 1, 2
• MRI is more sensitive than ultrasound for detecting smaller cysts, particularly in teenagers and young adults 1

Genetic Markers (Definitive Molecular Diagnosis)

Primary Genetic Markers

PKD1 and PKD2 are the primary genetic markers, accounting for approximately 95% of ADPKD cases (PKD1 ~80%, PKD2 ~15%). 4

A multigene panel approach is recommended over single-gene testing, including: 1

• PKD1 and PKD2 (major genes)
• PKHD1, HNF1B, DZIP1L (minor genes and phenocopies)
• Genes for other ciliopathies (NPHP, BBS genes)
• GANAB, DNAJB11, PRKCSH, TSC2, ALG5, ALG8, SEC63, CYS1 5, 4

Indications for Genetic Testing

Genetic testing is particularly valuable as a diagnostic marker in: 1, 3

• Few kidney cysts with suggestive clinical picture 1, 3
• Variable intrafamilial disease severity or very-early-onset disease 1
• Discordant imaging and glomerular filtration rate 1, 3
• Negative or indeterminate family history 1, 3, 6
• Young (<30 years) living-related kidney donors at risk 1, 2, 3
• Atypical renal or extrarenal findings 1

Prognostic Markers

Mayo Imaging Classification (MIC)

Once ADPKD is confirmed, height-adjusted total kidney volume (measured by MRI or CT) serves as a prognostic marker through the Mayo Imaging Classification. 1, 3

• The MIC stratifies typical ADPKD (class 1) into 5 risk groups (1A-1E) indicating accelerating kidney function decline 1, 3
• This marker is valid only for PKD1/PKD2 mutations, not minor genes 1
• Class 2 (atypical) presentations with unilateral or asymmetric cyst distribution require different interpretation 7

Important Diagnostic Pitfalls

A normal ultrasound does not exclude ADPKD in at-risk individuals <40 years, with negative predictive value of only ~90% for ages 18-29 years. 2

• After age 40, a normal ultrasound can exclude disease with near-100% certainty 2
• Repeat screening at intervals of ≥3 years is advised when initial ultrasound is normal in younger patients 2

These ultrasound and MRI criteria apply only to families with PKD1 or PKD2 mutations, not to minor gene variants. 1, 2

Several inherited diseases may mimic ADPKD with kidney/liver cysts (HNF1B-related disease, Alagille syndrome, TSC2 contiguous gene deletion), making genetic panel testing superior to imaging alone in atypical cases. 1, 8, 5