The effect of atrasentan on kidney and heart failure outcomes by baseline albuminuria and kidney function: a post hoc analysis of the SONAR randomized trial

Waijer, S. W. et al. (2021) The effect of atrasentan on kidney and heart failure outcomes by baseline albuminuria and kidney function: a post hoc analysis of the SONAR randomized trial. Clinical Journal of the American Society of Nephrology, 16(12), pp. 1824-1832. (doi: 10.2215/CJN.07340521) (PMID:34853062)

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Abstract

Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial. The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (<30, ≥30-45, and ≥45 ml/min per 1.73 m ) and UACR (<1000, ≥1000-3000, and ≥3000 mg/g). Atrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all interaction <0.01). The risk of heart failure hospitalization was higher in the atrasentan group (hazard ratio, 1.39; 95% confidence interval, 0.97 to 1.99) and was consistent across subgroups, with no evidence that relative or absolute risks differed across eGFR or UACR subgroups (all interaction >0.09). 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 category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups. Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532. [Abstract copyright: Copyright © 2021 by the American Society of Nephrology.]

Item Type:Articles
Keywords:Endothelin receptor antagonist, atrasentan, kidney outcome, heart failure, albuminuria, urinary tract physiological phenomena, hospitalization for heart failure.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Waijer, S. W., Gansevoort, R. T., Bakris, G. L., Correa-Rotter, R., Hou, F.-F., Kohan, D. E., Kitzman, D. W., Makino, H., McMurray, J. J.V., Perkovic, V., Tobe, S., Parving, H.-H., de Zeeuw, D., and Heerspink, H. J.L.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Clinical Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
ISSN:1555-9041
ISSN (Online):1555-905X
Published Online:07 December 2021

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