Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease

Abstract

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 m² for class 2Ae, and from -1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m² 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.

Keywords: ADPKD; clinical trial; kidney volume; risk factors.

Graphical abstract

Figure 1.

Coronal T2-weighted MRIs from two class 2Ae patients. Images show the regions included in the TKV determination before (left) and after (right) excluding exophytic cysts. (A) 35-year-old PKD1 woman whose baseline TKV reduced from 956 ml to 631 ml after exclusion of exophytic cysts, and (B) 42-year-old PKD1 man whose baseline TKV reduced from 2080 ml to 845 ml after exclusion of exophytic cysts.

Figure 2.

Flowchart of the study design and study participants. There were a total of 558 participants enrolled in the HALT-A study including 521 class 1 and 30 class 2A. Seven participants missing baseline htTKV records were excluded. Five class 2A patients without exophytic cysts were excluded. For the CKD stage analysis, 83 participants who died or were lost to follow-up (LTF) before reaching CKD end points were excluded, resulting in a total of 458 participants, including 23 class 2Ae participants, in the analysis. For the eGFR analysis, five participants whose eGFR was <60 at baseline were excluded, resulting in a total of 541 participants, including 25 class 2Ae participants, in the analysis.

Figure 3.

Mayo imaging classification of all participants, including class 2Ae and class1 participants with prominent exophytic cysts, before and after exclusion of exophytic cysts. The 541 class 1 participants were stratified into five subclasses (1A–1E) on the basis of their baseline htTKV and age. The htTKVs of each of the 25 class 2Ae participants are depicted by red points (before exclusion of exophytic cysts) and blue points (after exclusion of exophytic cysts) connected by red lines. With the recalculated htTKVs, 23 of 25 class 2Ae participants were downgraded to milder imaging classes (from red to blue data points): 4 (from 1E to 1D), 2 (from 1D to 1C), 1 (from 1D to 1B), 9 (from 1C to 1B), and 7 (from 1B to 1A). Two class 2Ae participants were unchanged in class (1B and 1C). The htTKVs of each of the 43 class 1 participants with prominent exophytic cysts are depicted by red and blue points connected by green lines. With the recalculated htTKVs, 14 of 43 class 1 participants with prominent exophytic cysts were downgraded by one subclass: 1 (from 1E to 1D), 3 (from 1D to 1C), 8 (from 1C to 1B), and 2 (from 1B to 1A). Twenty-nine participants were unchanged in class.

Figure 4.

Predicted probability of reaching CKD3 using original versus recalculated baseline htTKVs in unadjusted and adjusted models for (A) class 2Ae and (B) class 1 participants with prominent exophytic cysts. All data points are below the diagonal because htTKV has a positive coefficient and recalculated htTKVs are always less than the original htTKVs.

Figure 5.

eGFR trajectories. eGFR trajectories are shown for (A) class 1 participants only, (B) all and class 2Ae participants with original imaging classes, and (C) all, class 1, and class 2Ae participants with recalculated imaging classes. The data from class 1 only were used to fit the predicted curves, the trend of which was then assessed on the other groups of participants.