Abstract | INTRODUCTION: Patients with slowly progressive autosomal dominant polycystic kidney disease ( ADPKD) are unlikely to experience outcomes during randomized controlled trials (RCTs). An image classification of ADPKD into typical (diffuse cyst distribution) class 1A to E (by age- and height-adjusted total kidney volume [TKV]) and atypical (asymmetric cyst distribution) class 2 was proposed for prognostic enrichment design, recommending inclusion of only classes 1C to 1E in RCTs. METHODS: A post hoc exploratory analysis was conducted of the TEMPO 3:4 Trial, a prospective, randomized, double-blinded, controlled clinical trial in adult subjects with ADPKD, an estimated creatinine clearance >60 ml/min and total kidney volume >750 ml. RESULTS: Due to the entry criteria, the study population of TEMPO 3:4 was enriched for classes 1C-E (89.5 % of 1436 patients with baseline magnetic resonance images) compared to unselected populations (e.g., 60.5% of 590 Mayo Clinic patients). The effects of tolvaptan on TKV and eGFR slopes were greater in classes 1C to E than in 1B. In TEMPO 3:4, tolvaptan reduced TKV and eGFR slopes from 5.51% to 2.80% per year and from -3.70 to -2.78 ml/min/1.73 m2 per year, and lowered the risk for a composite endpoint of clinical progression events (hazard ratio = 0.87). Restricting enrollment to classes 1C to E would have reduced TKV and eGFR slopes from 5.78% to 2.91% per year and from -3.93 to -2.82 ml/min/1.73 m2 per year, and the risk of the composite endpoint (hazard ratio = 0.84, P = 0.003), with 10.5% fewer patients. DISCUSSION: Prognostic enrichment strategies such as the entry criteria used for TEMPO 3:4 or preferably the proposed image classification should be used in RCTs for ADPKD to increase power and to reduce cost.
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Authors | Maria V Irazabal, Jaime D Blais, Ronald D Perrone, Ron T Gansevoort, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, Peter C Harris, Wen Zhou, John Ouyang, Frank S Czerwiec, Vicente E Torres |
Journal | Kidney international reports
(Kidney Int Rep)
Vol. 1
Issue 4
Pg. 213-220
(Nov 2016)
ISSN: 2468-0249 [Print] United States |
PMID | 29142926
(Publication Type: Journal Article)
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