Abstract: SA-PO1189
Risk of CKD Progression in a Real-World Population Eligible for the ZENITH-High Proteinuria Trial
Session Information
- CKD: Biomarkers and Emerging Tools for Diagnosis and Monitoring
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Heerspink, Hiddo Jan L., University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- Pecoits-Filho, Roberto, Arbor Research Collaborative for Health, Ann Arbor, United States
- Ambery, Philip D., Clinical Late Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Adamsson Eryd, Samuel, Cardiovascular Renal and Metabolism Evidence Strategy, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden
- Lesén, Eva, Cardiovascular Renal and Metabolism Evidence Strategy, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden
- Nam, You-Seon, Cardiovascular, Renal and Metabolism Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, Maryland, United States
- Thuresson, Marcus, Statisticon AB, Uppsala, Sweden
- Perkovic, Vlado, The George Institute for Global Health, Sydney, New South Wales, Australia
Background
Previous data showed rapid deterioration in estimated glomerular filtration rate (eGFR) and high cardiorenal event rates in patients with proteinuric CKD (UACR >700 mg/g). The efficacy of zibotentan and dapagliflozin combination therapy in preserving eGFR in patients with UACR >700 mg/g is being explored in the ZENITH-High Proteinuria study (ZENITH-HP; NCT06087835). Here, we present data on eGFR decline and risks of other outcomes in a real-world population of patients meeting key eligibility criteria for ZENITH-HP.
Methods
Using USA healthcare claims data (Optum’s de-identified Clinformatics® Data Mart), we identified patients at their first UACR >700 mg/g or UPCR >1000 mg/g (index) between 1 January 2022 and 30 June 2022. Patients with eGFR <20 or ≥90 mL/min/1.73 m2, type 1 diabetes, kidney transplant, no RASi (ACEi or ARB) treatment within the last 120 days, heart failure (HF) hospitalization within the last 6 months, or on dialysis were excluded. Patients were followed for up to 2 years after index. Outcomes included eGFR slopes, risks of progression to kidney failure (diagnosis code, initiation of dialysis or confirmed eGFR <15), HF or CKD hospitalizations and atherosclerotic and cardiovascular (ASCVD) events (MI, stroke or PAD hospitalization) within 2 years after index.
Results
8534 patients (mean age: 72 years; 58% men) met the UACR or UPCR entry criteria for ZENITH-HP; 85% had type 2 diabetes, 26% had HF, and 15% had a previous MI. ACEi or ARBs were used by 46% and 55%, respectively, while use of SGLT-2 inhibitors was less common (7%). Median UACR and UPCR at index were 1361 mg/g and 2040 mg/g, respectively. Median eGFR was 44 mL/min/1.73 m2. Mean (median) eGFR decline was 4.7 (3.9) mL/min/1.73 m2/year. The risk of progression to kidney failure was 3.8% (95% CI 3.4–4.3) at year 1 and 10.6% (9.9–11.3) at year 2 after index. The 2-year risk of HF or CKD hospitalizations was 34.3% (33.2–35.4); the 2-year risk of ASCVD events was 10.7% (10.0–11.5).
Conclusion
This analysis confirms the significant risk of CKD progression and cardiorenal and ASCVD events in patients with proteinuric CKD meeting key eligibility criteria for ZENITH-HP, emphasizing the importance of improving access to guideline directed therapies and the need for novel therapies in this population.
Funding
- Commercial Support – AstraZeneca