Department Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Clin J Am Soc Nephrol. 2021 Dec;16(12):1824-1832. doi: 10.2215/CJN.07340521. Epub 2021 Dec 1.
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.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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.
阿曲生坦可降低肾衰竭风险，但会增加水肿风险，可能还会增加心力衰竭风险。严重 CKD 患者可能会从阿曲生坦治疗中获得更大的肾脏获益，但也可能面临更高的心力衰竭风险。我们根据 Study of Diabetic Nephropathy with Atrasentan（SONAR）试验中的基线估算肾小球滤过率（eGFR）和尿白蛋白/肌酐比值（UACR），对该试验中阿曲生坦治疗与安慰剂治疗的肾脏和心力衰竭事件的相对和绝对影响进行了分析。
设计、地点、参与者和测量方法：在 SONAR 试验中，我们对 3668 例患有 2 型糖尿病和伴有白蛋白尿升高的 CKD 患者进行了阿曲生坦与安慰剂的疗效比较。我们采用 Cox 比例风险回归分析研究了 eGFR（<30、≥30-45 和≥45 ml/min/1.73 m）和 UACR（<1000、≥1000-3000 和≥3000 mg/g）亚组中，阿曲生坦对主要肾脏结局（血肌酐翻倍、肾衰竭或肾脏死亡的复合终点）和心力衰竭住院的影响。
阿曲生坦治疗可使所有基线 eGFR 和 UACR 亚组的主要肾脏结局相对风险降低（风险比，0.71；95%置信区间，0.58 至 0.88；所有交互检验 P>0.21）。在 UACR 和 eGFR 最低的亚组中，主要肾脏结局发生率最高，患者获得的绝对获益最大（所有交互检验 P<0.01）。阿曲生坦组的心力衰竭住院风险较高（风险比，1.39；95%置信区间，0.97 至 1.99），且在各亚组中一致，无证据表明相对或绝对风险在 eGFR 或 UACR 亚组之间存在差异（所有交互检验 P>0.09）。
阿曲生坦可使主要肾脏结局的相对风险在基线 UACR 和 eGFR 亚组中持续降低。在 eGFR 最低和白蛋白尿最高的患者中，绝对风险降低幅度最大，这些患者的基线风险最高。相反，心力衰竭住院的相对和绝对风险在基线 UACR 和 eGFR 亚组中相似。阿曲生坦治疗糖尿病肾病研究（SONAR），NCT01858532。
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