Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease

Significance Statement Accurate prediction of risk for disease progression is crucial for clinical management of autosomal dominant polycystic kidney disease (ADPKD). The Mayo imaging classification of ADPKD uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk. Because the current Mayo classification applies only to patients with typical diffuse cystic disease (class 1) and poorly predicts eGFR decline for the remaining 5%?10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. The authors report an expanded imaging classification model in which use of a recalculated htTKV value that excludes prominent exophytic cysts improved prediction for eGFR trajectory. Using a recalculated htTKV may allow inclusion of class 2 patients in the Mayo classification of ADPKD and reclassification of class 1 patients with prominent exophytic cysts. Background The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%?10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. Methods Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. Results Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m(2) for class 2Ae, and from ?1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m(2) for class 1. Conclusions Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.