Background:Animal models implicate FGF-23 (fibroblast growth factor-23) as a direct contributor to adverse cardiorenal interactions such as sodium avidity, diuretic resistance, and neurohormonal activation, but this has not been conclusively demonstrated in humans. Therefore, we aimed to evaluate whether FGF-23 is associated with parameters of cardiorenal dysfunction in humans with heart failure, independent of confounding factors.Methods:One hundred ninety-nine outpatients with heart failure undergoing diuretic treatment at the Yale Transitional Care Center were enrolled and underwent blood collection, and urine sampling before and after diuretics.Results:FGF-23 was associated with several metrics of disease severity such as higher home loop diuretic dose and NT-proBNP (N-terminal pro-B-type natriuretic peptide), and lower estimated glomerular filtration rate, serum chloride, and serum albumin. Multivariable analysis demonstrated no statistically significant association between FGF-23 and sodium avidity measured by fractional excretion of sodium, or proximal or distal tubular sodium reabsorption, either before diuretic administration or at peak diuresis (P≥0.11 for all). Likewise, FGF-23 was not independently associated with parameters of diuretic resistance (diuretic excretion, cumulative urine and sodium output, and loop diuretic efficiency [P≥0.33 for all]) or neurohormonal activation (plasma or urine renin [P≥0.36 for all]). Moreover, the upper boundary of the 95% CI of all the partial correlations were ≤0.30, supporting the lack of meaningful correlations. FGF-23 was not associated with mortality in multivariable analysis (P=0.44).Conclusions:FGF-23 was not meaningfully associated with any cardiorenal parameter in patients with heart failure. While our methods cannot rule out a small effect, FGF-23 is unlikely to be a primary driver of cardiorenal interactions.

中文翻译：

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FGF-23（成纤维细胞生长因子-23）和心肾相互作用

背景：动物模型表明 FGF-23（成纤维细胞生长因子 23）是不良心肾相互作用的直接因素，例如钠亲和力、利尿剂抵抗和神经激素激活，但这尚未在人类身上得到最终证实。因此，我们旨在评估 FGF-23 是否与心力衰竭患者的心肾功能障碍参数相关，且不受混杂因素影响。方法：纳入耶鲁过渡护理中心接受利尿剂治疗的 199 名心力衰竭门诊患者。并在利尿剂之前和之后进行血液采集和尿液取样。结果：FGF-23 与疾病严重程度的几个指标相关，例如较高的家庭袢利尿剂剂量和 NT-proBNP（N 末端前 B 型利钠肽），并降低估计的肾小球滤过率、血清氯化物和血清白蛋白。多变量分析表明，在利尿剂给药前或利尿高峰期，FGF-23 与通过钠排泄分数或近端或远端肾小管钠重吸收测量的钠亲和力之间没有统计学意义的关联。所有P ≥ 0.11）。同样，FGF-23 与利尿剂抵抗参数（利尿剂排泄、累积尿和钠输出、袢利尿效率 [ P ≥0.33]）或神经激素激活（血浆或尿肾素 [ P ≥0.36 ]）。此外，所有偏相关的 95% CI 的上限≤0.30，支持缺乏有意义的相关性。多变量分析显示FGF-23与死亡率无关（P =0.44）。结论：FGF-23与心力衰竭患者的任何心肾参数均无显着相关性。虽然我们的方法不能排除小的影响，但 FGF-23 不太可能是心肾相互作用的主要驱动因素。