How does the Mayo imaging classification stage autosomal dominant polycystic kidney disease and guide treatment decisions, including the use of tolvaptan?

Mayo Imaging Classification for ADPKD: Risk Stratification and Treatment Guidance

Overview and Purpose

The Mayo Imaging Classification (MIC) uses height-adjusted total kidney volume (htTKV) and patient age to stratify ADPKD patients into five risk groups (1A through 1E), with classes 1C-1E identifying rapid progressors who require consideration for disease-modifying therapy such as tolvaptan. 1

The classification predicts both the rate of eGFR decline and timing of kidney failure, providing essential prognostic information to guide treatment decisions. 1, 2

Classification System Structure

Class 1 (Typical ADPKD)

• Characterized by bilateral, diffuse cystic involvement with mild to severe parenchymal replacement, where all cysts contribute similarly to total kidney volume 1
• Only Class 1 patients should be classified using MIC – the system is invalid for atypical presentations 1
• Subdivided into five risk groups (1A-1E) based on htTKV plotted against age on the Mayo nomogram 1

Class 2 (Atypical ADPKD)

• Comprises unilateral, segmental, asymmetric, or lopsided cyst distributions and bilateral disease with acquired atrophy 1
• htTKV has limited prognostic value in this group 1
• Represents approximately 5-10% of ADPKD patients 3
• These patients are older, less likely to have family history, less likely to have detectable PKD1/PKD2 mutations, and have significantly better renal prognosis 4

Risk Stratification by Class

Slow Progressors (Classes 1A-1B)

• Annual eGFR decline: -1.54 mL/min/year (1A) and -2.06 mL/min/year (1B) 5
• Annual kidney volume growth: 1.2%/year (1A) and 3.8%/year (1B) 5
• Lower risk of progression to kidney failure 2

Rapid Progressors (Classes 1C-1E)

• Annual eGFR decline: -3.58 mL/min/year (1C), -3.7 mL/min/year (1D), and -4.52 mL/min/year (1E) 5
• Annual kidney volume growth: 5.3%/year (1C), 9.4%/year (1D), and 11.7%/year (1E) 5
• These classes identify candidates for tolvaptan therapy based on accelerated disease progression 1, 2
• Hazard ratio for renal composite outcomes is 4.09 compared to slow progressors 5

Imaging Methodology

Preferred Modalities

• MRI or CT with automated/semi-automated volumetric tools provides the most accurate htTKV measurement 1
• The ellipsoid equation serves as an acceptable alternative calculation method 1
• Ultrasound-derived measurements are less precise but retain prognostic relevance 1

Measurement Technique

• Calculate total kidney volume from imaging 1
• Adjust for patient height to obtain htTKV 1
• Plot htTKV against patient age on the Mayo nomogram to assign risk class 1

Special Considerations for Exophytic Cysts

• Prominent exophytic cysts artificially inflate TKV measurements and should be excluded from calculations 1, 3
• Recalculating htTKV after excluding exophytic cysts improves specificity for predicting CKD stage 3 from 82.6% to 84.2% 3
• This adjustment reduces mean paired difference between predicted and observed eGFR from 17.6 to 4.0 mL/min/1.73 m² for Class 2Ae patients 3

Clinical Validation and Performance

Stability and Predictive Accuracy

• 82% of patients remain in their baseline Mayo class over time 6
• The classification successfully predicts kidney failure development, though sensitivity and positive predictive values are limited 6
• Observed eGFR decline matches predictions for classes 1A-1D, but is significantly slower than predicted for class 1E 6
• P10 accuracy (prediction within 10% of actual value) ranges from 37.5% to 59.5% in classes 1C-1E, indicating substantial individual variability 7

Important Limitations

• Marked interindividual variability exists within each class – not all patients in rapid progressor classes decline at the same rate 6
• The Mayo Clinic future eGFR equation may underestimate the actual rate of decline in classes 1C-1E 7
• A polynomial model allowing nonlinear eGFR decline provides more accurate predictions than linear models 6

Contraindications to MIC Use

Do not apply MIC in the following scenarios: 1

• Atypical imaging patterns (Class 2) where htTKV poorly predicts eGFR decline
• Patients with pathogenic variants in genes other than PKD1 or PKD2
• Cases with prominent exophytic cysts unless TKV is recalculated excluding these cysts

Integration with Treatment Decisions

Tolvaptan Eligibility

• Classes 1C-1E identify rapid progressors who are candidates for tolvaptan therapy based on their accelerated eGFR decline and earlier progression to kidney failure 1, 2
• The classification provides objective, imaging-based criteria to support treatment initiation decisions 2

Genetic Considerations

• PKD1 mutations cause more severe disease with kidney failure typically in the fifth decade 8
• PKD2 mutations lead to kidney failure typically in the seventh decade 8
• Genetic testing is recommended when imaging shows few cysts, when disease severity varies within families, or for evaluation of potential living kidney donors 2, 8

Common Pitfalls to Avoid

• Never apply MIC to Class 2 (atypical) patients – the prognostic value is invalid in this population 1
• Do not assume all patients within a given class will progress at identical rates – individual variability is substantial 6
• Avoid using original TKV measurements when prominent exophytic cysts are present – recalculate excluding these cysts 1, 3
• Do not rely solely on ultrasound for precise volumetric assessment when MRI or CT is available 1
• Remember that up to 10% of ADPKD cases arise from de novo mutations, so negative family history does not exclude the diagnosis 8