Kidney Week

Abstract: PO2376

The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function: A Post Hoc Analysis of the SONAR Trial

Session Information

• CKD: Insights from Recent Clinical Trials and Large Real-World Effectiveness Studies
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Waijer, Simke W., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Simke W. Waijer, PharmD

• Gansevoort, Ron T., Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Ron T. Gansevoort,

• Bakris, George L., The University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris,

• Correa-Rotter, Ricardo, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, DF, Mexico

Ricardo Correa-Rotter,

• Hou, Fan Fan, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China

Fan Fan Hou,

• Kohan, Donald E., University of Utah Health, Salt Lake City, Utah, United States

Donald E. Kohan,

• Makino, Hirofumi, Okayama Daigaku, Okayama, Okayama, Japan

Hirofumi Makino,

• McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom

John McMurray,

• Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia

Vlado Perkovic,

• Tobe, Sheldon W., Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Sheldon W. Tobe,

• Parving, Hans-Henrik, Rigshospitalet, Kobenhavn, Denmark

Hans-Henrik Parving,

• de Zeeuw, Dick, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Dick de Zeeuw,

• L Heerspink, Hiddo Jan, Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

Background

Atrasentan reduces kidney failure risk, but increases risk of edema and possibly heart failure in patients with diabetic kidney disease. Patients with advanced chronic kidney disease (CKD) may obtain greater absolute renal benefit from atrasentan but may be at higher risk of fluid retention due to impaired renal excretory capacity. We assessed effects of atrasentan on kidney and heart failure events according to baseline eGFR and albumin:creatinine ratio (UACR) in a post-hoc analysis of the SONAR trial.

Methods

The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated UACR was examined in SONAR. We used Cox regression to study effects on the primary kidney outcome (doubling of serum creatinine, end-stage kidney disease or renal death) and heart failure hospitalization across subgroups of eGFR (<30, ≥30-45, ≥45 ml/min/1.73m²) and UACR (<1000, ≥1000-3000, ≥3000 mg/g).

Results

Atrasentan reduced the relative risk of the primary kidney outcome (HR 0.71, 95%CI 0.58-0.88) consistently across subgroups of baseline eGFR and UACR (table). Patients in the highest UACR and lowest eGFR subgroups showed the largest absolute benefit (all P-interaction <0.01). The relative (HR 1.39, 95%CI 0.97-1.99) and absolute risk of heart failure hospitalization was consistent across eGFR or UACR subgroups (all P-interaction >0.09).

Conclusion

Atrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria subgroup who were at highest baseline risk. However, the relative and absolute risk of heart failure hospitalization were similar across baseline UACR and eGFR subgroups. These results support the initiation of atrasentan in high risk patients with CKD and significant albuminuria.