Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1-2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison with Magnetic Resonance Imaging.

BACKGROUND AND OBJECTIVES: Total kidney volume is a validated prognostic biomarker for autosomal dominant polycystic kidney disease. Total kidney volume by magnetic resonance imaging (MRI) and manual segmentation is considered the "reference standard," but it is time consuming and not readily accessible. By contrast, three-dimensional (3D) ultrasound provides a promising technology for total kidney volume measurements with unknown potential. Here, we report a comparative study of total kidney volume measurements by 3D ultrasound versus the conventional methods by ultrasound ellipsoid and MRI ellipsoid. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This single-center prospective study included 142 patients who completed a standardized 3D ultrasound and MRI. Total kidney volumes by 3D ultrasound and ultrasound ellipsoid were compared with those by MRI. We assessed the agreement of total kidney volume measurements by Bland-Altman plots and misclassification of the Mayo Clinic imaging classes between the different imaging methods, and we assessed prediction of Mayo Clinic imaging classes 1C-1E by average ultrasound kidney length >16.5 cm. RESULTS: Compared with MRI manual segmentation, MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid underestimated total kidney volume (mean difference: -3%, -9%, and -11%, respectively), with Mayo Clinic imaging classes misclassified in 11%, 21%, and 22% of patients, respectively; most misclassified cases by MRI ellipsoid (11 of 16), 3D ultrasound (23 of 30), and ultrasound ellipsoid (26 of 31) were placed into a lower Mayo Clinic imaging class. Predictions of the high-risk Mayo Clinic imaging classes (1C-1E) by MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid all yielded high positive predictive value (96%, 95%, and 98%, respectively) and specificity (96%, 96%, and 99%, respectively). However, both negative predictive value (90%, 88%, and 95%, respectively) and sensitivity (88%, 85%, and 94%, respectively) were lower for 3D ultrasound and ultrasound ellipsoid compared with MRI ellipsoid. An average ultrasound kidney length >16.5 cm was highly predictive of Mayo Clinic imaging classes 1C-1E only in patients aged ≤45 years. CONCLUSIONS: Total kidney volume measurements in autosomal dominant polycystic kidney disease by 3D ultrasound and ultrasound ellipsoid displayed similar bias and variability and are less accurate than MRI ellipsoid. Prediction of high-risk Mayo Clinic imaging classes (1C-1E) by all three methods provides high positive predictive value, but ultrasound ellipsoid is simpler to use and more readily available.