Supplementary Material for: Urinary cell cycle arrest biomarkers and diuretic efficiency in acute heart failure

Introduction
This study aimed to evaluate the association between the NephroCheck ® Test AKIRisk® Score, diuretic efficiency (DE) and the odds of worsening kidney function (WKF) within the first 72 hours of admission in patients hospitalized for acute heart failure (AHF).
Methods
The study prospectively enrolled 125 patients admitted with AHF. NephroCheck ® Test
was obtained within the first 24 of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents.
Results
The median AKIRisk® Score was 0.11 (IQR 0.06-0.34) and 38 (30.4%) patients had an AKIRisk® Score >0.3. The median cumulative DE at 72 hours was 1963 mL (IQR 1317-3239 ml). At 72 hours, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariate setting, there was an inverse association between the AKIRisk® Score and DE within the first 72 hours. In fact, the highest the AKIRisk® Score (centered at 0.3) the higher the likelihood of poor diuretic efficiency (below the median) and WKF at 72 hours (Odds Ratio [OR] 2.04; 95%; CI 1.02-4.07; p=0.043, and OR 3.31, 95% CI 1.30-8.43; p = 0.012, respectively).
Conclusion
In patients with AHF, a higher NephroCheck ® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 hours. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario.

引言
本研究旨在评估因急性心力衰竭（acute heart failure, AHF）住院的患者中，NephroCheck®检测AKIRisk®评分、利尿效率（diuretic efficiency, DE）与入院后72小时内肾功能恶化（worsening kidney function, WKF）发生风险之间的关联。

方法
本研究前瞻性纳入125例急性心力衰竭住院患者，于入院后24小时内完成NephroCheck®检测。利尿效率定义为每40mg呋塞米等效剂量对应的净液体尿量。

结果
AKIRisk®评分的中位数为0.11（四分位距0.06~0.34），其中38例（30.4%）患者的AKIRisk®评分＞0.3。入院72小时时的累积利尿效率中位数为1963mL（四分位距1317~3239mL）。至72小时时，共有10例（8%）患者出现血清肌酐（serum creatinine, sCr）绝对值升高≥0.5mg/dL，即发生肾功能恶化。多变量分析模型显示，入院后72小时内AKIRisk®评分与利尿效率呈负相关。具体而言，以0.3为中心的AKIRisk®评分越高，患者出现低利尿效率（低于中位数水平）及72小时内肾功能恶化的风险越高（对应比值比[OR]分别为2.04；95%置信区间1.02~4.07；P=0.043，以及OR=3.31，95%置信区间1.30~8.43；P=0.012）。

结论
在急性心力衰竭患者中，更高的NephroCheck® AKIRisk®评分与更低的利尿效率及72小时内更高的肾功能恶化风险相关。未来仍需开展进一步研究，以明确尿液细胞周期阻滞生物标志物在急性心力衰竭场景中的作用。