Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany.
Department of Internal Medicine, University Medical Center Rostock, Schillingallee 35, 18057 Rostock, Germany.
Medicina (Kaunas). 2022 Dec 2;58(12):1780. doi: 10.3390/medicina58121780.
Background and Objectives: Albumin binding of the loop diuretic furosemide forms the basis for its transport to the kidney and subsequent tubular secretion, which is a prerequisite for its therapeutic effects. Accordingly, high albumin concentrations should result in higher efficacy of furosemide. However, study results on the combination of furosemide in conjunction with albumin, and on the efficacy of furosemide in hypoalbuminemia, did not confirm this hypothesis. The aim of this study was to determine the efficacy of furosemide not only in relation to albumin concentration, but also taking albumin function into account. Materials and Methods: In a prospective and non-interventional clinical observational trial, blood and urine samples from 50 intensive care patients receiving continuous intravenous furosemide therapy were evaluated. Albumin binding capacity (ABiC) determination allowed conclusions to be drawn about the binding site-specific loading state of albumin, by quantifying the unbound fraction of the fluorescent marker dansylsarcosine. In addition, assessment of the total concentration of furosemide in plasma and urine, as well as the concentration of free furosemide fraction in plasma, was performed by HPLC−MS. The efficacy of furosemide was evaluated by the ratio of urine excretion to fluid intake. Results: In patients with an ABiC ≥ 60% free furosemide fraction was significantly lower compared to patients with a lower ABiC (p < 0.001), urinary furosemide concentration was higher (p = 0.136), and a significantly higher proportion of infused furosemide was excreted renally (p = 0.010). ABiC was positively correlated (r = 0.908, p = 0.017) with increase in the urine excretion to fluid input ratio after initiation of furosemide therapy. Conclusions: ABiC could serve as a marker for individual response to furosemide and could be used to generate patient-specific therapeutic regimens. In view of the relatively low number of patients in this study, the relationship between furosemide efficacy and albumin function should be investigated in larger studies in the future.
袢利尿剂呋塞米与白蛋白的结合是其转运至肾脏并随后进行管状分泌的基础，这是其治疗效果的前提。因此，高白蛋白浓度应导致呋塞米的疗效更高。然而，关于呋塞米与白蛋白联合使用以及在低白蛋白血症中呋塞米疗效的研究结果并未证实这一假设。本研究的目的不仅是确定呋塞米的疗效与白蛋白浓度有关，还要考虑白蛋白的功能。
在一项前瞻性、非干预性临床观察性试验中，评估了 50 名接受连续静脉注射呋塞米治疗的重症监护患者的血液和尿液样本。白蛋白结合能力（ABiC）的测定通过定量荧光标记物dansylsarcosine 的未结合部分，可以得出关于白蛋白结合部位特定的载药状态的结论。此外，通过 HPLC-MS 测定了血浆和尿液中呋塞米的总浓度以及血浆中游离呋塞米分数的浓度。通过尿排泄与液体摄入的比值评估呋塞米的疗效。
在 ABiC≥60%的患者中，游离呋塞米分数明显低于 ABiC 较低的患者（p<0.001），尿中呋塞米浓度较高（p=0.136），并且输注的呋塞米中有更高比例经肾脏排泄（p=0.010）。ABiC 与呋塞米治疗开始后尿排泄与液体输入比值的增加呈正相关（r=0.908，p=0.017）。
ABiC 可以作为个体对呋塞米反应的标志物，并可用于制定患者特异性治疗方案。鉴于本研究中患者数量相对较少，未来应在更大规模的研究中进一步探讨呋塞米疗效与白蛋白功能之间的关系。
