Abstract: TH-PO387
The Predicting Renal Outcomes in Polycystic Kidney Disease (PROPKD) Score for Estimating Risk of Rapid Progression and Treatment Benefit in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Session Information
- Genetic Diseases of the Kidneys: Cystic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1101 Genetic Diseases of the Kidneys: Cystic
Authors
- Fomin, Vitalay, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States
- Jiang, Huan, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States
- Roth, Sharin, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, New Jersey, United States
Background
The PROPKD scoring system for ADPKD demonstrated its utility for identifying patients at risk of rapid progression to loss of kidney function in a post hoc analysis of the TEMPO 3:4 trial (Cornec-LeGall Nephrol Dial Transplant 2018). Given that TEMPO 3:4 enrolled a relatively young cohort (18–50 years) with early chronic kidney disease (>80% in stages G1–G2), we evaluated PROPKD for predicting disease progression and tolvaptan benefit in a broader population that included subjects in the REPRISE trial (Torres N Engl J Med 2017), who were older (18–65 years) with more advanced disease (95% in stages G3-G4).
Methods
Per PROPKD scoring, subjects were assigned points for male sex (+1), hypertension (+2) or first urologic event before age 35 (+2), and mutation (PKD2: 0; non-truncating PKD1: +2; truncating PKD1: +4). For subjects <35 years without hypertension or urologic events, 0 was assigned to these variables and overall score calculated as the sum of the remaining factors. Total score ranged from 0–9, with 0–3 low risk (LR), 4–6 intermediate risk (IR), and 7–9 high risk (HR) for rapid progression. Annualized decline in estimated GFR (eGFR; mL/min/1.73 m2/yr) was calculated by regressing eGFR against time by subject from month 1 to month 12 in REPRISE, and from week 3 to month 36 in TEMPO 3:4, to exclude the early hemodynamic effect of tolvaptan.
Results
A population of 210 LR, 548 IR, and 430 HR was analyzed. Whereas there were no significant differences in annualized eGFR decline between risk groups among tolvaptan-treated subjects (LR -2.57, IR -2.69, HR -2.86), in untreated (placebo) subjects, decline was more rapid in higher risk groups (LR -2.82, IR -3.49, HR -4.04; P<0.01 for HR vs LR). Tolvaptan had a significant treatment effect vs placebo for IR and HR, but not LR (Table).
Conclusion
In a population with a broad spectrum of disease characteristics, the PROPKD scoring system predicted rapidity of eGFR decline in untreated ADPKD and supported the benefit of tolvaptan in patients at elevated risk of rapid progression.
Table. Annualized eGFR decline by PROPKD risk group and treatment in TEMPO 3:4 and REPRISE
| Low Risk | Intermediate Risk | High Risk | ||||
| Tolvaptan (n=126) | Placebo (n=84) | Tolvaptan (n=326) | Placebo (n=222) | Tolvaptan (n=244) | Placebo (n=186) | |
| Change in eGFR (mL/min/1.73 m2) | -2.57 | -2.82 | -2.69 | -3.49 | -2.86 | -4.04 |
| P-value for difference between treatments | 0.6184 | 0.0102 | 0.0033 | |||
| Relative treatment effect | 8.7% | 22.9% | 29.2% | |||
Funding
- Commercial Support – Otsuka Pharmaceutical Development & Commercialization Inc.