How does the Mayo Clinic autosomal dominant polycystic kidney disease (ADPKD) imaging classification work, and how is it used to stratify risk and guide tolvaptan (Jynarque) therapy?

Mayo Clinic Imaging Classification for ADPKD

The Mayo Imaging Classification (MIC) uses height-adjusted total kidney volume (htTKV) and patient age to stratify ADPKD patients into five risk groups (1A-1E) that predict the rate of kidney function decline, with classes 1C-1E identifying rapid progressors who experience accelerated eGFR loss and earlier progression to kidney failure. 1

How the Classification System Works

Two Main Categories

The MIC divides ADPKD into two fundamental classes 1:

• Class 1 (Typical ADPKD): Bilateral and diffuse cystic distribution with mild, moderate, or severe replacement of kidney tissue, where all cysts contribute similarly to total kidney volume 1
• Class 2 (Atypical ADPKD): Includes unilateral, segmental, asymmetric, or lopsided cyst patterns, plus bilateral presentations with acquired atrophy 1

Critical limitation: Prognostic information from the MIC is valid ONLY for Class 1 patients with typical imaging findings 1. The classification should not be applied to patients with pathogenic variants in genes other than PKD1 or PKD2 1.

The Five Risk Subgroups (Class 1A-1E)

For typical ADPKD (Class 1), patients are stratified into five subgroups based on their htTKV plotted against age 1:

• Class 1A: Slowest progression, minimal kidney growth
• Class 1B: Slow progression
• Class 1C: Moderate-rapid progression (defines transition to "rapid progressor")
• Class 1D: Rapid progression
• Class 1E: Most rapid progression, highest risk

Rapid progressors (Classes 1C-1E) demonstrate significantly faster eGFR decline compared to slow progressors (1A-1B), with annual eGFR losses of -3.58, -3.7, and -4.52 mL/min/year for classes 1C, 1D, and 1E respectively, versus -1.54 and -2.06 mL/min/year for classes 1A and 1B 2.

Measurement Methodology

Imaging Modalities

MRI or CT scan provides the most accurate htTKV measurement using automated or semi-automated volumetric tools 1. The ellipsoid equation can be used as an alternative calculation method 1.

Ultrasound-determined total kidney volume and kidney length are less precise but retain prognostic value 1. However, in pediatric populations, the adult Mayo classification strongly underestimates disease severity even with height correction 3.

Calculation Steps

1. Measure total kidney volume (TKV) in milliliters using cross-sectional imaging
2. Adjust for patient height: htTKV = TKV ÷ height (in meters)
3. Plot htTKV against patient age on the Mayo classification nomogram
4. Assign the appropriate class (1A-1E) based on where the patient falls on the curve 1

Clinical Application and Risk Stratification

Predicting Kidney Function Decline

The MIC effectively predicts both the rate of eGFR decline and timing of kidney failure 1, 4. Classes 1C-1E identify patients at highest risk who should be prioritized for disease-modifying therapy 4.

Annual kidney volume growth rates (mHTKV-α) accelerate progressively: 1.2% per year in class 1A, 3.8% in 1B, 5.3% in 1C, 9.4% in 1D, and 11.7% in 1E 2. The MIC class independently predicts renal composite outcomes (doubling of serum creatinine, 50% eGFR decline, or initiation of renal replacement therapy) with a hazard ratio of 4.09 for rapid progressors 2.

Guiding Tolvaptan Therapy

The MIC serves as the primary tool for identifying ADPKD patients who qualify for and will benefit most from tolvaptan (Jynarque) therapy 4. Patients classified as rapid progressors (1C-1E) represent the population most likely to experience clinically meaningful benefit from vasopressin V2 receptor antagonist therapy, as these individuals face accelerated progression to kidney failure without intervention 1, 2.

Important Caveats and Pitfalls

When NOT to Use the MIC

Do not apply the Mayo classification in these scenarios 1:

• Atypical imaging patterns (Class 2 ADPKD) - htTKV poorly predicts eGFR decline in these patients 5, 6
• Pathogenic variants in genes other than PKD1 or PKD2 1
• Prominent exophytic cysts that artificially inflate TKV measurements 6

Patients with atypical polycystic kidney disease by imaging represent only 8.8% of ADPKD cases but have distinctly better prognosis, with lower likelihood of progression to advanced CKD 5. These patients are older, less likely to have family history or detectable PKD1/PKD2 mutations, and should not be risk-stratified using the standard MIC approach 5.

Accuracy Considerations

While the MIC effectively identifies risk groups, individual eGFR predictions using the Mayo Clinic equation show reduced accuracy (P10 accuracy 37.5-59.5%) in rapid progressor classes 7. The equation may underestimate the actual rate of eGFR decline in classes 1C-1E 7. Therefore, use the classification primarily for risk stratification rather than precise individual eGFR trajectory prediction 7.

Special Populations

For patients with prominent exophytic cysts, recalculating htTKV to exclude these cysts improves prediction accuracy and allows appropriate classification 6. This refinement increases specificity for predicting CKD stage 3 development from 82.6% to 84.2% and reduces the mean difference between predicted and observed eGFR 6.